Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PTK2 (PTK2 protein tyrosine kinase 2)

Written2011-03Joerg Schwock, Neesha Dhani
Department of Laboratory Medicine, Pathobiology, Division of Anatomical Pathology, University of Toronto, 1 King's College Circle, 6th Floor, Toronto, Ontario M5S 1A8, Canada (JS); University Health Network, Princess Margaret Hospital, Division of Medical Oncology, Hematology, Institute of Medical Sciences, University of Toronto, Princess Margaret Hospital/Ontario Cancer Institute, 610 University Ave., Room: 7-113, Toronto, Ontario M5G 2M9, Canada (ND)

(Note : for Links provided by Atlas : click)


HGNC (Hugo) PTK2
HGNC Alias symbFAK
HGNC Alias nameprotein phosphatase 1, regulatory subunit 71
HGNC Previous namePTK2 protein tyrosine kinase 2
LocusID (NCBI) 5747
Atlas_Id 41898
Location 8q24.3  [Link to chromosome band 8q24]
Location_base_pair Starts at 140657900 and ends at 141001282 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PTK2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AGO2 (8q24.3)::PTK2 (8q24.3)DLGAP3 (1p34.3)::PTK2 (8q24.3)HOXB3 (17q21.32)::PTK2 (8q24.3)
PTDSS1 (8q22.1)::PTK2 (8q24.3)PTK2 (8q24.3)::ANKRD11 (16q24.3)PTK2 (8q24.3)::BSN (3p21.31)
PTK2 (8q24.3)::CACNG8 (19q13.42)PTK2 (8q24.3)::CLTC (17q23.1)PTK2 (8q24.3)::NCR3 (6p21.33)
PTK2 (8q24.3)::NEXMIF (Xq13.3)PTK2 (8q24.3)::PKHD1L1 (8q23.1)PTK2 (8q24.3)::PPP2R5E (14q23.2)
PTK2 (8q24.3)::PTK2 (8q24.3)PTK2 (8q24.3)::RNF139 (8q24.13)PTK2 (8q24.3)::SLC45A4 (8q24.3)
PTK2 (8q24.3)::SMAP2 (1p34.2)PTK2 (8q24.3)::TRAPPC9 (8q24.3)PTK2 (8q24.3)::TSNARE1 (8q24.3)
PTK2 (8q24.3)::UBE2H (7q32.2)PTK2 (8q24.3)::UGT2A3 (4q13.2)SP3 (2q31.1)::PTK2 (8q24.3)
TRAPPC9 (8q24.3)::PTK2 (8q24.3)


Note Cloning of the FAK cDNA and initial characterization of the kinase was accomplished independently by three groups in 1992 (Schaller et al., 1992; Hanks et al., 1992; Guan and Shalloway 1992). The cDNA of the human FAK homologue was first cloned by André and Becker-André (1993). The position of the human PTK2 gene encoding FAK on chromosome 8 was first predicted by Fiedorek and Kay (1995).
Transcription Initial expression studies using reverse transcriptase PCR detected FAK mRNA in a series of lymphoid cell lines as well as HeLa and SK-N-SH neuroblastoma cells indicating ubiquitous expression. Only a lymphocyte adhesion deficient cell line tested negative for the FAK transcript (André and Becker-André 1993). Transcripts of different sizes were detected in different human tissues in the same study with differential expression patterns for these transcripts noted in brain, lung, heart, liver and placenta.
Several transcript variants encoding different FAK isoforms have been found for the PTK2 gene. The full-length nature of the following three has been determined.

- Variant 1 differs in the 5' UTR and coding sequence compared to variant 2. The resulting isoform (a) is shorter at the N-terminus compared to isoform (b).
4414 bp - 33 exons - 1065 aa.
Ave. residue weight: 113.521.
Charge: 3.5.
Isoelectric point: 6.7311.
Molecular weight: 120899.54.
Number of residues: 1065.

- Variant 2 encodes the longest isoform (b).
4286 bp - 31 exons - 1073 aa.
Ave. residue weight: 113.366.
Charge: 2.0.
Isoelectric point: 6.6317.
Molecular weight: 121641.45.
Number of residues: 1073.

- Variant 3 differs in the 5' UTR and coding sequence, and contains two additional in-frame segments near the 3' end of the coding sequence, compared to variant 2. The resulting isoform (c) is shorter at the N-terminus and contains two additional segments in the C-terminus compared to isoform b.


Note Focal adhesion kinase (FAK) is a cytoplasmic non-receptor protein tyrosine kinase which was isolated for the first time by co-immunoprecipitation of tyrosine-phosphorylated proteins from cells transformed with Rous sarcoma virus v-Src (Kanner et al., 1990).
Description FAK is a ubiquitously expressed protein composed of a N-terminal FERM domain (protein 4.1, ezrin, radixin, moesin), a kinase domain, three intervening proline-rich regions (PRR) and a C-terminal focal adhesion targeting (FAT) domain (Figure 1).
  Figure 1: Schematic of focal adhesion kinase domain structure with phosphorylation sites.
Expression Ubiquitous.
Localisation Cytoplasmic and nuclear.
  Figure 2: Immunohistochemical staining of FAK in invasive cancer of the uterine cervix. (Note the accentuation of the FAK staining at the margin of the tumor nests. Size bar, 1 mm). Method and antibody: Schwock et al., 2009.
Function FAK is characterized by a functional duality, serving as a kinase as well as a molecular scaffold. These two functions may be required independently or in concert depending on the context in which FAK-mediated signaling occurs (Sieg et al., 1999; Sieg et al., 2000). FAK regulates the dynamic of focal adhesion complexes which are sites of attachment between cells and extracellular matrix. Cyclic assembly and disassembly of these complexes at the leading and trailing edge of the cell is required for the migration of mesenchymal cells and those that adopt mesenchymal-like characteristics as a consequence of developmental processes or during disease states. The latter mainly encompasses forms of tissue repair (i.e. wound healing and fibrosis) as well as neoplasia (i.e. tumor invasion and metastasis). As an example, Figure 2 shows immunohistochemical staining for FAK in metastatic cancer of the uterine cervix. FAK has been implicated with the establishment of a front-back polarity (Tilghman et al., 2005), lamellipodial persistence at the leading edge (Owen et al., 2007) and release of adhesions at the trailing edge (Iwanicki et al., 2008).
Integrin engagement with the extracellular matrix results in integrin clustering and a sequence of inter- and intramolecular events that permit the autophosphorylation of FAK at Tyr397 (Dunty et al., 2004). Subsequent recruitment of Src-family kinases through SH2-domain binding is followed by a mutual activation of both kinases. In the case of FAK this further activation is accomplished by phosphorylation of other tyrosine residues, specifically Tyr407, 576, 577, 861 and 925. Phosphorylation of Tyr576 and 577 increases FAK kinase activity whereas the remaining tyrosine residues serve as docking sites for SH2-containing factors such as Grb2 which links FAK into the MAPK pathway. Tyr397 also constitutes a docking site for the p85 subunit of PI3K (Chen and Guan, 1994) and phospholipase C gamma (Zhang et al., 1999). The PRRs are sites of interaction with SH3-containing factors which transmit signals downstream of the kinase and regulate the activity of Rho-family GTPases in charge of cell motility through the formation of stress fibres (RhoA), lamellipodia (Rac) and filopodia (Cdc42). Crk-associated substrate (p130Cas), initially identified in a two-hybrid screen, is one of the main downstream factors that bind to the PRRs of FAK (Polte and Hanks, 1995). Signaling via p130Cas towards Crk, DOCK180 and Rac has been linked to membrane ruffling, lamellipodia formation and cell motility (Harte et al., 1996; Cho and Klemke, 2002). A second essential downstream target of FAK is paxillin (Bellis et al., 1995), an adaptor protein lacking intrinsic kinase activity which can be phosphorylated at two sites, Tyr31 and Tyr118, and binds FAK within the C-terminal focal adhesion targeting (FAT) region (Hayashi et al., 2002). Mutations in FAK that disrupt binding to paxillin affect the localization of the kinase to focal contacts. Paxillin may also be involved in regulation of MAPK downstream signaling due to an overlapping binding site with Grb2 which binds to Tyr925 within the FAT region (Liu et al., 2002).
More recent studies link FAK to the regulation of cell-cell contacts, microtubule stability and control of gene transcription. Conflicting results have been reported from different experimental systems implicating FAK either with the dissolution (Avizienyte et al., 2002; Cicchini et al., 2008) or the promotion (Yano et al., 2004; Playford et al., 2008) of cell-cell contacts which suggests a dependency of this feature on the specific cellular context. Ezratty et al. (2005) reported on the role of FAK, Grb2 and dynamin in microtubule-induced focal adhesion disassembly. Earlier studies demonstrated an integrin-mediated activation of FAK at the leading edge of migrating cells as requirement for microtubule stabilization mediated by Rho and mDia (Palazzo et al., 2004). This mechanism also involves localization of a lipid raft marker, ganglioside GM1, to the leading edge. Xie et al. (2003) showed that Cdk5-mediated serine-phosphorylation of FAK was linked to the localization of the kinase at microtubule fork structures which contribute to nuclear repositioning in migrating neuronal cells. Recently, serine-phosphorylated FAK was shown to co-localize with centrosomes in mitotic endothelial cells. In this study by Park et al. (2009), FAK was also found associated with cytoplasmic dynein, and deletion of FAK resulted in mitotic defects. In 2005, Golubovskaya et al. reported results indicating a physical interaction between the N-terminal fragment of FAK and the N-terminal transactivation domain of p53. This interaction led to suppression of p53-mediated apoptosis and inhibition of the transcriptional activity of p53. Lim et al. (2008) subsequently provided data demonstrating a scaffolding role of nuclear FAK for MDM2-mediated p53 degradation mediated by the different lobes of the FERM domain. Also, basic sequences in the F2 lobe of the FERM domain were implicated in the nuclear localization of FAK (Lim et al., 2008), but alternative mechanisms independent from this putative nuclear localization signal are thought to exist (Schaller, 2010). Another nuclear function was recently uncovered by Luo et al. (2009) who described a role of FAK in chromatin remodelling via its interaction with MBD2 leading to increased myogenin expression and muscle-terminal differentiation. Liu et al. (2004), Li et al. (2004) and Ren et al. (2004) reported an involvement of FAK in netrin-1 signaling downstream of the netrin receptor DCC with consequences for axonal outgrowth and guidance in the developing brain.
- Mouse Models
Several mouse models have been generated to elucidate the functions of FAK both during normal development and neoplasia. A role of FAK in embryonal development was first observed in fak-/- mice which displayed defects in mesoderm development and anterior-posterior axis formation with embryonic lethality around day E8.5 (Ilic et al., 1995).
A conditional knockout model using a Cre-loxP system with Cre recombinase under the control of the nkx2-5 promoter was generated by Hakim et al. (2007). The major abnormality reported from this study was a profound disturbance of the development of the cardiac outflow tract. Knockout mice from this study died shortly after birth and displayed a range of cardiac defects which resemble the human congenital heart defects Tetralogy of Fallot and persistent truncus arteriosus. Peng et al. (2006) and DiMichele et al. (2006) reported results obtained with conditional knockout mice which carried Cre-recombinase under the control of the myosin light chain 2v promoter. Peng et al. (2006) found that knockout mice developed eccentric cardiac hypertrophy upon stimulation with angiotensin II or pressure overload. In contrast, the results by DiMichele et al. (2006) suggest that FAK functions to promote cardiac hypertrophy. In a later study by Peng at al. (2008) with myosin light chain-2a Cre mice they observed cardiac developmental abnormalities with thin ventricular walls and ventricular septal defects in the knockout mice, the majority of which died in the embryonic stage. Endothelial cell-specific knockout of FAK, again using a Cre-loxP approach, has been reported by Shen et al. (2005) and Braren et al. (2006). The observed phenotypes in knockout mice from both studies strongly suggest a role of FAK in vascular morphogenesis, particularly vascular remodelling and sprouting angiogenesis. The roles of FAK in the cardiovascular system were reviewed by Vadali et al. (2007).
A series of mouse models suggest an essential role of FAK during the development of the central nervous system. Beggs et al. (2003) created dorsal forebrain-specific conditional knockout mice using the Cre/loxP approach and observed an essential function of FAK for the formation of a normal basal lamina at the interface between radial glial end-feet and meningeal fibroblasts. They noted that the cortical changes seen in their study resembled lissencephaly phenotypes seen in some forms of human congenital muscular dystrophy.
Van Miltenburg et al. (2009) investigated the role of FAK in normal mammary gland using a conditional FAK-knockout mammary epithelial cell transplantation model based on FAK(lox/lox)/Rosa26Cre-ERT2 donor mice with loss of FAK in all mammary cells. They observed an abnormal mammary duct development with a disruption of myoepithelial and luminal epithelial cell layer and aberrant ductal morphogenesis during pregnancy.
Comprehensive reviews focused on the cellular functions of FAK have been published by Mitra et al. (2005) and Schaller (2010). Figure 3 schematically summarizes some of the diverse cellular functions of FAK.
- Regulation
The level of FAK expression is negatively and positively regulated by several transcription factors including p53, NF-kB and N-Myc (Golubovskaya et al., 2004; Beierle et al., 2007). Aside from the tyrosine residues implicated with FAK activation, at least four different serine phosphorylation sites (Ser722, 840, 843 and 910) have been recognized within FAK. Although the function of these serine sites has been examined less comprehensively, their phosphorylation has generally been associated with FAK inactivation, such as during mitosis (Ma et al., 2001), in suspension and under conditions that disturb the integrity of the actin cytoskeleton (Jacamo et al., 2007). FAK signaling is subject to additional levels of regulation which involve proteolytic cleavage (Dourdin et al., 2001), sumoylation (Kadaré et al., 2003), inhibition by FAK family interacting protein of 200 kDa (FIP200) (Abbi et al., 2002), dephosphorylation by protein-tyrosine phosphatases (Zeng et al., 2003), and generation of alternatively spliced isoforms such as FAK-related non-kinase (FRNK) (Schaller et al., 1993).
- Other protein family members: Pyk2.
  Figure 3: Schematic of the Cellular Functions of FAK.
Homo sapiens PTK2
% Identity for
vs. Pan troglodytes PTK2
vs. Canis lupus familiaris PTK2
vs. Mus musculus Ptk2
vs. Rattus norvegicus Ptk2
vs. Gallus gallus PTK2
vs. Danio rerio ptk2.1
vs. Drosophila melanogaster Fak56D
vs. Caenorhabditis elegans kin-32
(Source :

Implicated in

Entity Neoplasia
Note Increased expression of FAK was first noticed in high-grade and metastatic sarcomas (Weiner et al., 1994) and later in pre-invasive as well as invasive epithelial neoplasms (Owens et al., 1995). In general, lower levels of FAK expression are found in normal tissues whereas the higher levels are present in metastatic cancer suggesting an involvement of the kinase in oncogenesis. In neoplastic conditions the kinase has been credited with a range of functions including tumor cell motility (Sieg et al., 1999), matrix degradation leading to distant spread (Hauck et al., 2002), suppression of apoptosis (Sonoda et al., 2000), anoikis (Frisch et al., 1996) and senescence (Pylayeva et al., 2009) as well as positive effects on angiogenesis (Mitra et al., 2006), vasculogenic mimicry (Hess et al., 2005) and hypoxia response (Skuli et al., 2009). Results from a Cre/loxP-mediated FAK-knockout model specific to mouse mammary epithelial cells revealed a reduced pool of cancer stem/progenitor cells after FAK deletion which suggests that the kinase may not only support tumor cell dissemination to distant sites, but also the colonization of the target organ and establishment of a new tumor mass (Luo et al., 2009). Other transgenic mouse models focused on the role of FAK in neoplasia have been reported by McLean et al. (2004) for skin and by Lahlou et al. (2007), Provenzano et al. (2008) and Pylayeva et al. (2009) for mammary tumor formation and progression.
Entity Nervous system
Note The role of FAK in glioma tumor progression and in the regulation of the permeability of tumor-associated vasculature has been described, as well as the therapeutic efficacy of FAK inhibition by both pharmacologic compounds and liposomal-mediated RNA interference (Shi et al., 2007; Lipinski et al., 2008; Lee et al., 2010; Wang et al., 2011). Immunohistochemical analysis of 96 patient biopsies demonstrated higher levels of total and phosphorylated FAK in high grade tumors which correlated with inferior patient survival (Ding et al., 2010).
Beierle et al. (2007) reported on the relevance of FAK as cellular survival factor in N-myc-amplified neuroblastoma and identified N-myc binding sites in the FAK promoter. Recently, the same group also provided data indicating greater in vivo-therapeutic efficacy of pharmacologic FAK inhibition in N-myc-positive model systems (Beierle et al., 2010a; Beierle et al., 2010b). Efficacy of a novel small molecule dual IGF1R/FAK tyrosine kinase inhibitor (TAE226) leading to decreased FAK phosphorylation and cellular viability, cell cycle arrest and apoptosis has been described in human neuroblastoma cell lines (Beierle et al., 2008b). FAK expression was demonstrated in 51 of 70 clinical neuroblastoma samples by immunohistochemistry. FAK protein levels correlated with mRNA transcript levels and with advanced disease stage in this study (Beierle et al., 2008a).
Entity Head and neck squamous cell carcinoma
Note FAK has been linked to invasion in squamous cell carcinoma of the head and neck through promotion of cell motility and MMP-2 production (Canel et al., 2008). FAK gene and protein expression were previously evaluated in 211 clinical samples which included tissue from cases of dysplasia and benign hyperplasia (Canel et al., 2006). In this study, 62% of the primary cancers had high FAK protein expression, and the levels were consistent with those seen in corresponding lymph node metastases. A recent preclinial study has implicated FAK phosphorylation levels with radioresistance (Hehlgans et al., 2009).
Entity Thyroid carcinoma
Note Immunohistochemical staining of 108 patient samples for FAK protein discriminated malignant from benign thyroid lesions. FAK levels correlated with tumor size and capsular/lymphatic invasion (Michailidi et al., 2010). Previously, Kim et al. (2004) reported FAK expression in follicular, papillary, medullary and anaplastic thyroid carcinomas. FAK was not expressed in normal thyroid tissue and nodular hyperplasia, but in some of the follicular adenomas included in their study.
Entity Breast cancer
Note Lahlou et al. (2007) reported a block in tumor progression in a transgenic mouse model of breast cancer with disrupted FAK function based on Cre/loxP recombination. An earlier immunohistochemical study on clinical breast tissue showed increased FAK expression in ductal carcinoma in situ compared to atypical ductal hyperplasia and invasive ductal carcinoma (Lightfoot et al., 2004). The authors of this study concluded that FAK overexpression precedes tumor cell invasion and metastasis. Subsequently, a study by Lark et al. (2005) in 629 breast cancer samples correlated high FAK protein expression with poor prognostic indicators such as high mitotic index and nuclear grade, negative hormone receptor status, and Her2/neu over-expression. Schmitz et al. (2005) provided further evidence to support Her2/neu downstream signaling through FAK/Src-mediated pathways. Recently, a positive correlation between FAK over-expression and p53 mutation status has been reported (Golubovskaya et al., 2008; Golubovskaya et al., 2009). Yom et al. (2010) evaluated 435 cases of invasive ductal cancer for FAK gene copy number by fluorescence in situ hybridization (FISH) and FAK protein expression by immunohistochemistry, both of which correlated with features of aggressive tumor biology. Concordance between FISH and immunohistochemistry results was observed in 74.9%. An increased gene copy number by FISH correlated significantly with inferior patient outcome in this study.
Entity Lung cancer
Note Array comparative genomic hybridization studies on clinical samples of small cell lung cancer demonstrated regions of copy number alternations (gains and losses) enriched for genes involved in focal adhesion signaling. This included gains of FAK copy number which was confirmed in a smaller subset of the original 46 cases by FISH and quantitative RT-PCR. FAK was also highly expressed in tumor tissue (90% of 52 samples) in comparison with normal lung samples (Ocak et al., 2010). Wang et al. (2009) reported results of their study focused on FAK expression in bronchio-alveolar carcinoma (BAC) and lung adenocarcinomas. They found that in lung adenocarcinoma overall survival was better for patients with FAK-negative compared with FAK-positive tumors. A study by Hiratsuka et al. (2011) implicated endothelial FAK and E-selectin with the formation of lung metastasis from distant primary tumors due to the formation of discrete foci of vascular hyper-permeability important for the initial homing of metastatic cancer cells to the lungs.
Entity Gastro-intestinal tract cancer
Note Giaginis et al. (2009) reported results of an immunohistochemical study performed on the two major subtypes of gastric adenocarcinoma, including 30 cases of intestinal- and 36 cases of diffuse-type. Although FAK staining in diffuse-type gastric cancer correlated with larger tumor size and advanced disease stage, it also correlated with longer overall survival. For intestinal type cancer, however, an association with increased proliferative capacity and a non-significant trend to inferior survival was reported. A retrospective study including 444 surgical samples demonstrated a positive correlation between FAK gene amplification and protein expression levels with tumor size, lymphovascular invasion and nodal/distant metastases (Park et al., 2010). Focal adhesion kinase protein expression and gene amplification were positively correlated with each other in this study, and each of them was found to be an independent poor prognostic factor.
FAK has been implicated in invasion and metastasis as well as chemoresistance in pancreatic cancer (Duxbury et al., 2003; Duxbury et al., 2004). FAK overexpression by immunohistochemistry, demonstrated in 24 of 50 (48%) patient samples, correlated with tumor size, but no other features including grade, lymph node involvement or metastasis in a study by Furuyama et al. (2006). Another study included an examination of both FAK and Src protein levels. FAK expression correlated significantly with tumor stage while Src expression correlated with both tumor stage and patient survival, and was identified as an independent prognostic factor by multivariate analysis (Chatzizacharias et al., 2010).
Hayashi et al. (2010) demonstrated high levels of cytoplasmic FAK expression in normal biliary epithelium and observed a gradual loss of staining from dysplasia to extra-hepatic bile duct carcinoma. In this study, positive FAK staining was associated with a significantly better survival. Increased levels of FAK mRNA and protein have also been observed in a study of 60 patients with hepatocellular cancers. Increased mRNA levels correlated with tumor size, serum AFP and inferior disease-free and overall survival (Fujii et al., 2004).
RNA interference studies in colorectal cancer cell line xenografts demonstrated that FAK inhibition resulted in inhibition of cell proliferation and angiogenesis, induction of apoptosis and tumor growth suppression (Lei et al., 2010). Elevated levels of FAK mRNA and protein were noted in a small cohort of 34 matched primary colon cancers and liver metastases (Lark et al., 2003). More recently a larger series of colorectal cancers with matched liver metastases was used to evaluate the correlation of FAK staining with clinical outcome. In this study, FAK staining was equivalent in primary and metastatic lesions, and elevated levels of FAK and Src were associated with a reduced time to recurrence (de Heer et al., 2008).
Entity Female genital tract cancer
Note FAK has been implicated in the invasive and metastatic phenotype of ovarian cancer through multiple pathways (Hu et al., 2008; Yagi et al., 2008). In one report, MUC4-induced epithelial-mesenchymal transition was partially mediated by FAK, and pharmacologic FAK inhibition successfully abrogated MUC4-induced cell motility (Ponnusamy et al., 2010). In another study, cooperative signaling of c-met and alpha5beta1 integrin through FAK/Src was associated with promotion of invasion and metastases (Mitra et al., 2010). FAK activation also appears to be relevant to the development of resistance to standard cytotoxics (Halder et al., 2005; Villedieu et al., 2006) and preclinical studies have demonstrated therapeutic efficacy of various methods of FAK inhibition including pharmacologic inhibition and RNA interference (Halder et al., 2006; Halder et al., 2007; Yang et al., 2007). Sood et al. (2010) recently described protection from anoikis by catecholamine signaling mediated by FAK. They concluded that these results support a role for FAK signaling in the stress-mediated promotion of aggressive tumor biology. They also demonstrated increased levels of FAK and phosphorylated FAK in greater than 50% of the examined tumors, both of which correlated with inferior patient survival. Two earlier studies documented up-regulation of FAK protein and phosphorylated FAK in invasive ovarian cancers in comparison with normal epithelium (Sood et al., 2004; Grisaru-Granovsky et al., 2005). Sood et al. (2004) also noted associations between FAK immunohistochemical staining and more advanced tumor stage, tumor grade, metastasis and inferior overall survival.
Immunohistochemical analysis of 134 cases of endometrial cancer demonstrated moderate to strong staining in the majority (89%) of cases. Weak FAK staining was noted in the remaining 11% and associated with a trend to improved survival. Increased FAK staining, however, correlated with measures of poor outcome including tumor grade, lymphovascular invasion and lymph node metastases (Gabriel et al., 2009). A different study demonstrated high levels of FAK expression in endometrial cancers of different histologies (endometrioid, serous and clear cell) as well as in regions of endometrial hyperplasia. The authors concluded that their data implicate FAK in endometrial carcinogenesis (Livasy et al., 2004).
An analysis of 166 surgical samples demonstrated cytoplasmic and membranous FAK staining in regions of cervical dysplasia and frankly invasive cancer of the uterine cervix with absent staining in adjacent normal cervical epithelium (Gabriel et al., 2006). One third of the patients, with tumors exhibiting weak FAK staining, had an inferior survival compared to those with moderate/strong FAK staining, and weak FAK staining correlated with lymph node positivity in this study. Oktay et al. (2003) demonstrated positive FAK staining in premalignant lesions. Similarly, Schwock et al. (2009) demonstrated an increase in FAK expression and concurrent decrease of E-cadherin in metastatic cervical cancer and carcinoma in-situ compared to normal cervical epithelium. An association between E-cadherin loss and FAK was also noted in an earlier study that included 26 carcinomas and 5 carcinoma in situ cases (Moon et al., 2003). Although FAK protein expression remained constant in this study, elevated levels of phosphorylated FAK were found in carcinoma samples.
Entity Male genital tract cancer
Note FAK has been linked with aggressive tumor behavior in models of androgen-independent prostate cancer (Johnson et al., 2008). An early study comparing normal and hyperplastic prostatic tissue with localized and advanced prostate cancers demonstrated increased levels of total and activated FAK in more advanced disease (Tremblay et al., 1996). Association of FAK with paxillin and p50csk was noted in cases of metastatic cancer. Rovin et al. (2002) described increased FAK expression in pre-malignant lesions that was maintained at different stages of tumor progression. A study by Zheng et al. (1999) proposed that the migratory behavior of prostate cancer cells is related to the de novo expression of alphaVbeta3 integrin with signaling through FAK.
Entity Genito-urinary tract cancer
Note Increased levels of FAK and paxillin mRNA transcript have been noted in metastasizing renal carcinoma cell lines in comparison with normal renal cortex epithelial cells (Jenq et al., 1996). FAK/Src signaling was also demonstrated to be relevant to the aggressive behavior of bladder carcinoma cells in vitro, and inhibition of the phosphatase HD-PTP resulted in an enhanced FAK phosphorylation and increased cell motility (Mariotti et al., 2009).
Entity Skin cancer
Note Preclinical studies have implicated FAK with the promotion of an aggressive melanoma phenotype through its effects on invasion and migration (Hess et al., 2005; Hess and Hendrix 2006; Smit et al., 2007; Kaneda et al., 2008; Sun et al., 2009). FAK also has importance early in the metastatic dissemination of melanoma cells (Abdel-Ghany et al., 2002). A study by Smith et al. (2005) demonstrated that downregulation of FAK by antisense oligonucleotide sensitizes melanoma cells to 5-fluorouracil treatment. A preliminary clinical report suggests that FAK may function as a universal tumor-associated antigen that could be exploited for cancer immunotherapy including melanoma (Kobayashi et al., 2009). A recent study by Trimmer et al. (2010) reported reduced levels of caveolin-1 in clinical metastases of melanoma as well as in highly metastatic melanoma cell lines. They demonstrated that caveolin-1 expression in B16F10 melanoma cells promotes cell proliferation while suppressing invasion and migration via FAK/Src.
McLean et al. (2004) demonstrated a role for FAK in the malignant progression from papilloma to squamous cell carcinoma in a transgenic mouse model combined with chemical carcinogenesis. No effect of the FAK deletion was noted on wound re-epithelialization.
Entity Soft tissues, bone and hemato-lymphoid tissues
Note Yui et al. (2010) developed a highly metastatic osteosarcoma cell line through in vivo selection which, in comparison with the parental line, demonstrated higher levels of activated FAK and cdc42. Hanada et al. (2005) showed localization of phosphorylated FAK at the infiltrative edge in a three dimensional culture model using invasive murine fibrosarcoma cells. In the same study, expression of FAK-related non-kinase (FRNK) inhibited experimental metastases in syngenic mice without significant effects on primary tumor growth. In a study on bone metastasis, the dual FAK/Pyk2 inhibitor PF-271 suppressed the growth of experimental intra-tibial tumors in rats and restored tumor-induced bone loss (Bagi et al., 2008).
Immunohistochemical analysis of normal and neoplastic hemato-lymphoid tissues demonstrated FAK staining in B cells of the germinal center, marginal and mantle zones (Ozkal et al., 2009). Corresponding staining was present in most B-cell lymphomas while T-cell lymphomas were predominantly negative. Neoplastic cells of classical Hodgkin's lymphoma were negative for FAK while those of lymphocyte-predominant Hodgkin's lymphoma were positive in the same study.
A study of 60 primary acute myeloid leukemia samples demonstrated FAK transcript and protein expression in 48% cases and Pyk2 expression in 81% cases (Recher et al., 2004). FAK-positive acute myeloid leukemia cells displayed a higher migratory efficiency and lower sensitivity to chemotherapy. FAK expression positively correlated with white blood count at diagnosis, death rate and median survival.
Entity Non-neoplastic disorders
Note Shahrara et al. (2007) reported on the elevated expression of phosphorylated FAK, Pyk2 and other signaling molecules, in synovial tissues of patients with rheumatoid or osteoarthritis. They postulated that FAK signaling may be important for the recruitment of inflammatory cells into susceptible joints and required to promote the disease process.
Chen et al. (2001) found that keratinocytes from patients with psoriasis have elevated levels of phosphorylated FAK and concluded that integrin/FAK signaling contributes to a 'pre-activation' of uninvolved keratinocytes that predisposes to the development of psoriatic plaques in response to certain stimuli.
FAK has a role in the development of the cardiovascular system since FAK-null mice are embryonically lethal with phenotypic abnormalities approximating those seen in human congenital heart defects (Vadali et al., 2007). FAK also appears to be involved cardiac hypertrophy and heart failure through its involvement in the cardiac response to biochemical stress and hypertrophic agonists. The relevance of FAK to cardiac physiology likely differs with the cellular context. Although FAK activation has been suggested to accelerate function deterioration of an overloaded heart, selective FAK deletion in cardiomyoctes has also been associated with maladaptive cardiac remodeling (Franchini et al., 2009).
FAK appears to be essential for normal glucose transport and glycogen synthesis due to cross talk between integrin and insulin signaling pathways (Huang et al., 2002; Huang et al., 2006). FAK has also been implicated in hyperglycemia-related vascular complications in Diabetes mellitus (Mori et al., 2002). Two independent studies reported on increased levels of activated FAK in the glomeruli from diabetic rats that could be abrogated by insulin treatment (Clark et al., 1995; Shikano et al., 1996).
FAK signaling has been implicated with non-neoplastic renal disease. Holzapfel et al. (2007) documented a role for FAK during restoration of tubular integrity in renal ischemia and reperfusion, and an earlier study by Morino et al. (1999) indicated activated FAK-signaling during the development and progression of autoimmune-mediated nephritis in an animal model.


Regulation of focal adhesion kinase by a novel protein inhibitor FIP200.
Abbi S, Ueda H, Zheng C, Cooper LA, Zhao J, Christopher R, Guan JL.
Mol Biol Cell. 2002 Sep;13(9):3178-91.
PMID 12221124
Focal adhesion kinase activated by beta(4) integrin ligation to mCLCA1 mediates early metastatic growth.
Abdel-Ghany M, Cheng HC, Elble RC, Pauli BU.
J Biol Chem. 2002 Sep 13;277(37):34391-400. Epub 2002 Jul 10.
PMID 12110680
Expression of an N-terminally truncated form of human focal adhesion kinase in brain.
Andre E, Becker-Andre M.
Biochem Biophys Res Commun. 1993 Jan 15;190(1):140-7.
PMID 8422239
Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling.
Avizienyte E, Wyke AW, Jones RJ, McLean GW, Westhoff MA, Brunton VG, Frame MC.
Nat Cell Biol. 2002 Aug;4(8):632-8.
PMID 12134161
Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases.
Bagi CM, Roberts GW, Andresen CJ.
Cancer. 2008 May 15;112(10):2313-21.
PMID 18348298
FAK deficiency in cells contributing to the basal lamina results in cortical abnormalities resembling congenital muscular dystrophies.
Beggs HE, Schahin-Reed D, Zang K, Goebbels S, Nave KA, Gorski J, Jones KR, Sretavan D, Reichardt LF.
Neuron. 2003 Oct 30;40(3):501-14.
PMID 14642275
Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines.
Beierle EA, Ma X, Trujillo A, Kurenova EV, Cance WG, Golubovskaya VM.
Mol Carcinog. 2010b Mar;49(3):224-34.
PMID 19885861
Characterization of tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase.
Bellis SL, Miller JT, Turner CE.
J Biol Chem. 1995 Jul 21;270(29):17437-41.
PMID 7615549
Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation.
Braren R, Hu H, Kim YH, Beggs HE, Reichardt LF, Wang R.
J Cell Biol. 2006 Jan 2;172(1):151-62.
PMID 16391003
Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression.
Canel M, Secades P, Garzon-Arango M, Allonca E, Suarez C, Serrels A, Frame M, Brunton V, Chiara MD.
Br J Cancer. 2008 Apr 8;98(7):1274-84. Epub 2008 Mar 18.
PMID 18349846
Evaluation of the clinical significance of focal adhesion kinase and SRC expression in human pancreatic ductal adenocarcinoma.
Chatzizacharias NA, Giaginis C, Zizi-Serbetzoglou D, Kouraklis GP, Karatzas G, Theocharis SE.
Pancreas. 2010 Aug;39(6):930-6.
PMID 20431421
Basal keratinocytes from uninvolved psoriatic skin exhibit accelerated spreading and focal adhesion kinase responsiveness to fibronectin.
Chen G, McCormick TS, Hammerberg C, Ryder-Diggs S, Stevens SR, Cooper KD.
J Invest Dermatol. 2001 Dec;117(6):1538-45.
PMID 11886520
Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase.
Chen HC, Guan JL.
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10148-52.
PMID 7937853
Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold.
Cho SY, Klemke RL.
J Cell Biol. 2002 Feb 18;156(4):725-36. Epub 2002 Feb 11.
PMID 11839772
TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling.
Cicchini C, Laudadio I, Citarella F, Corazzari M, Steindler C, Conigliaro A, Fantoni A, Amicone L, Tripodi M.
Exp Cell Res. 2008 Jan 1;314(1):143-52. Epub 2007 Sep 18.
PMID 17949712
Increased phosphorylation of focal adhesion kinase in diabetic rat kidney glomeruli.
Clark S, Muggli E, La Greca N, Dunlop ME.
Diabetologia. 1995 Oct;38(10):1131-7.
PMID 8690164
Myocyte-restricted focal adhesion kinase deletion attenuates pressure overload-induced hypertrophy.
DiMichele LA, Doherty JT, Rojas M, Beggs HE, Reichardt LF, Mack CP, Taylor JM.
Circ Res. 2006 Sep 15;99(6):636-45. Epub 2006 Aug 10.
PMID 16902179
Expression of focal adhesion kinase and phosphorylated focal adhesion kinase in human gliomas is associated with unfavorable overall survival.
Ding L, Sun X, You Y, Liu N, Fu Z.
Transl Res. 2010 Jul;156(1):45-52. Epub 2010 May 26.
PMID 20621036
Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts.
Dourdin N, Bhatt AK, Dutt P, Greer PA, Arthur JS, Elce JS, Huttenlocher A.
J Biol Chem. 2001 Dec 21;276(51):48382-8. Epub 2001 Oct 15.
PMID 11602605
FERM domain interaction promotes FAK signaling.
Dunty JM, Gabarra-Niecko V, King ML, Ceccarelli DF, Eck MJ, Schaller MD.
Mol Cell Biol. 2004 Jun;24(12):5353-68.
PMID 15169899
Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells.
Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE.
Surgery. 2004 May;135(5):555-62.
PMID 15118593
Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase.
Ezratty EJ, Partridge MA, Gundersen GG.
Nat Cell Biol. 2005 Jun;7(6):581-90. Epub 2005 May 15.
PMID 15895076
Mapping of the focal adhesion kinase (Fadk) gene to mouse chromosome 15 and human chromosome 8.
Fiedorek FT Jr, Kay ES.
Mamm Genome. 1995 Feb;6(2):123-6.
PMID 7766995
Focal adhesion kinase signaling in cardiac hypertrophy and failure.
Franchini KG, Clemente CF, Marin TM.
Braz J Med Biol Res. 2009 Jan;42(1):44-52. (REVIEW)
PMID 19219296
Control of adhesion-dependent cell survival by focal adhesion kinase.
Frisch SM, Vuori K, Ruoslahti E, Chan-Hui PY.
J Cell Biol. 1996 Aug;134(3):793-9.
PMID 8707856
Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be served as an independent prognostic factor.
Fujii T, Koshikawa K, Nomoto S, Okochi O, Kaneko T, Inoue S, Yatabe Y, Takeda S, Nakao A.
J Hepatol. 2004 Jul;41(1):104-11.
PMID 15246215
Clinical significance of focal adhesion kinase in resectable pancreatic cancer.
Furuyama K, Doi R, Mori T, Toyoda E, Ito D, Kami K, Koizumi M, Kida A, Kawaguchi Y, Fujimoto K.
World J Surg. 2006 Feb;30(2):219-26.
PMID 16425085
Expression of focal adhesion kinase in patients with endometrial cancer: a clinicopathologic study.
Gabriel B, Hasenburg A, Waizenegger M, Orlowska-Volk M, Stickeler E, zur Hausen A.
Int J Gynecol Cancer. 2009 Oct;19(7):1221-5.
PMID 19823058
Weak expression of focal adhesion kinase (pp125FAK) in patients with cervical cancer is associated with poor disease outcome.
Gabriel B, zur Hausen A, Stickeler E, Dietz C, Gitsch G, Fischer DC, Bouda J, Tempfer C, Hasenburg A.
Clin Cancer Res. 2006 Apr 15;12(8):2476-83.
PMID 16638855
Expression and clinical significance of focal adhesion kinase in the two distinct histological types, intestinal and diffuse, of human gastric adenocarcinoma.
Giaginis CT, Vgenopoulou S, Tsourouflis GS, Politi EN, Kouraklis GP, Theocharis SE.
Pathol Oncol Res. 2009 Jun;15(2):173-81. Epub 2008 Nov 6.
PMID 18987997
FAK overexpression and p53 mutations are highly correlated in human breast cancer.
Golubovskaya VM, Conway-Dorsey K, Edmiston SN, Tse CK, Lark AA, Livasy CA, Moore D, Millikan RC, Cance WG.
Int J Cancer. 2009 Oct 1;125(7):1735-8.
PMID 19521985
Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples.
Grisaru-Granovsky S, Salah Z, Maoz M, Pruss D, Beller U, Bar-Shavit R.
Int J Cancer. 2005 Jan 20;113(3):372-8.
PMID 15455382
Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation.
Guan JL, Shalloway D.
Nature. 1992 Aug 20;358(6388):690-2.
PMID 1379699
Conditional deletion of focal adhesion kinase leads to defects in ventricular septation and outflow tract alignment.
Hakim ZS, DiMichele LA, Doherty JT, Homeister JW, Beggs HE, Reichardt LF, Schwartz RJ, Brackhan J, Smithies O, Mack CP, Taylor JM.
Mol Cell Biol. 2007 Aug;27(15):5352-64. Epub 2007 May 25.
PMID 17526730
Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy.
Halder J, Kamat AA, Landen CN Jr, Han LY, Lutgendorf SK, Lin YG, Merritt WM, Jennings NB, Chavez-Reyes A, Coleman RL, Gershenson DM, Schmandt R, Cole SW, Lopez-Berestein G, Sood AK.
Clin Cancer Res. 2006 Aug 15;12(16):4916-24.
PMID 16914580
Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells.
Halder J, Landen CN Jr, Lutgendorf SK, Li Y, Jennings NB, Fan D, Nelkin GM, Schmandt R, Schaller MD, Sood AK.
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8829-36.
PMID 16361572
Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma.
Halder J, Lin YG, Merritt WM, Spannuth WA, Nick AM, Honda T, Kamat AA, Han LY, Kim TJ, Lu C, Tari AM, Bornmann W, Fernandez A, Lopez-Berestein G, Sood AK.
Cancer Res. 2007 Nov 15;67(22):10976-83.
PMID 18006843
Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis.
Hanada M, Tanaka K, Matsumoto Y, Nakatani F, Sakimura R, Matsunobu T, Li X, Okada T, Nakamura T, Takasaki M, Iwamoto Y.
Clin Exp Metastasis. 2005;22(6):485-94.
PMID 16320111
Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin.
Hanks SK, Calalb MB, Harper MC, Patel SK.
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8487-91.
PMID 1528852
p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase.
Harte MT, Hildebrand JD, Burnham MR, Bouton AH, Parsons JT.
J Biol Chem. 1996 Jun 7;271(23):13649-55.
PMID 8662921
FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth.
Hauck CR, Hsia DA, Puente XS, Cheresh DA, Schlaepfer DD.
EMBO J. 2002 Dec 2;21(23):6289-302.
PMID 12456636
Decreased expression of focal adhesion kinase is associated with a poor prognosis in extrahepatic bile duct carcinoma.
Hayashi A, Aishima S, Inoue T, Nakata K, Morimatsu K, Nagai E, Oda Y, Tanaka M, Tsuneyoshi M.
Hum Pathol. 2010 Jun;41(6):859-66. Epub 2010 Feb 25.
PMID 20185162
The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin.
Hayashi I, Vuori K, Liddington RC.
Nat Struct Biol. 2002 Feb;9(2):101-6.
PMID 11799401
3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226.
Hehlgans S, Lange I, Eke I, Cordes N.
Radiother Oncol. 2009 Sep;92(3):371-8. Epub 2009 Sep 2.
PMID 19729215
Focal adhesion kinase signaling and the aggressive melanoma phenotype.
Hess AR, Hendrix MJ.
Cell Cycle. 2006 Mar;5(5):478-80. Epub 2006 Mar 1.
PMID 16552181
Focal adhesion kinase promotes the aggressive melanoma phenotype.
Hess AR, Postovit LM, Margaryan NV, Seftor EA, Schneider GB, Seftor RE, Nickoloff BJ, Hendrix MJ.
Cancer Res. 2005 Nov 1;65(21):9851-60.
PMID 16267008
Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation.
Hiratsuka S, Goel S, Kamoun WS, Maru Y, Fukumura D, Duda DG, Jain RK.
Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3725-30. Epub 2011 Feb 14.
PMID 21321210
Role of focal adhesion kinase (FAK) in renal ischaemia and reperfusion.
Holzapfel K, Neuhofer W, Bartels H, Fraek ML, Beck FX.
Pflugers Arch. 2007 Nov;455(2):273-82. Epub 2007 Jun 5.
PMID 17549512
Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase.
Hu XW, Meng D, Fang J.
Carcinogenesis. 2008 Dec;29(12):2369-76. Epub 2008 Oct 28.
PMID 18974065
Focal adhesion kinase (FAK) regulates insulin-stimulated glycogen synthesis in hepatocytes.
Huang D, Cheung AT, Parsons JT, Bryer-Ash M.
J Biol Chem. 2002 May 17;277(20):18151-60. Epub 2002 Jan 23.
PMID 11809746
Reduced expression of focal adhesion kinase disrupts insulin action in skeletal muscle cells.
Huang D, Khoe M, Ilic D, Bryer-Ash M.
Endocrinology. 2006 Jul;147(7):3333-43. Epub 2006 Mar 30.
PMID 16574795
Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice.
Ilic' D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T.
Nature. 1995 Oct 12;377(6549):539-44.
PMID 7566154
FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts.
Iwanicki MP, Vomastek T, Tilghman RW, Martin KH, Banerjee J, Wedegaertner PB, Parsons JT.
J Cell Sci. 2008 Mar 15;121(Pt 6):895-905. Epub 2008 Feb 26.
PMID 18303050
FAK phosphorylation at Ser-843 inhibits Tyr-397 phosphorylation, cell spreading and migration.
Jacamo R, Jiang X, Lunn JA, Rozengurt E.
J Cell Physiol. 2007 Feb;210(2):436-44.
PMID 17096371
Integrin expression on cell adhesion function and up-regulation of P125FAK and paxillin in metastatic renal carcinoma cells.
Jenq W, Cooper DR, Ramirez G.
Connect Tissue Res. 1996;34(3):161-74.
PMID 9023046
Focal adhesion kinase controls aggressive phenotype of androgen-independent prostate cancer.
Johnson TR, Khandrika L, Kumar B, Venezia S, Koul S, Chandhoke R, Maroni P, Donohue R, Meacham RB, Koul HK.
Mol Cancer Res. 2008 Oct;6(10):1639-48.
PMID 18922979
PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation.
Kadare G, Toutant M, Formstecher E, Corvol JC, Carnaud M, Boutterin MC, Girault JA.
J Biol Chem. 2003 Nov 28;278(48):47434-40. Epub 2003 Sep 18.
PMID 14500712
Mutation of Y925F in focal adhesion kinase (FAK) suppresses melanoma cell proliferation and metastasis.
Kaneda T, Sonoda Y, Ando K, Suzuki T, Sasaki Y, Oshio T, Tago M, Kasahara T.
Cancer Lett. 2008 Nov 8;270(2):354-61. Epub 2008 Jul 7.
PMID 18606490
Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases.
Kanner SB, Reynolds AB, Vines RR, Parsons JT.
Proc Natl Acad Sci U S A. 1990 May;87(9):3328-32.
PMID 2110361
Increased expression of focal adhesion kinase in thyroid cancer: immunohistochemical study.
Kim SJ, Park JW, Yoon JS, Mok JO, Kim YJ, Park HK, Kim CH, Byun DW, Lee YJ, Jin SY, Suh KI, Yoo MH.
J Korean Med Sci. 2004 Oct;19(5):710-5.
PMID 15483349
Focal adhesion kinase as an immunotherapeutic target.
Kobayashi H, Azumi M, Kimura Y, Sato K, Aoki N, Kimura S, Honma M, Iizuka H, Tateno M, Celis E.
Cancer Immunol Immunother. 2009 Jun;58(6):931-40. Epub 2008 Oct 22.
PMID 18941742
Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression.
Lahlou H, Sanguin-Gendreau V, Zuo D, Cardiff RD, McLean GW, Frame MC, Muller WJ.
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20302-7. Epub 2007 Dec 3.
PMID 18056629
High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype.
Lark AL, Livasy CA, Dressler L, Moore DT, Millikan RC, Geradts J, Iacocca M, Cowan D, Little D, Craven RJ, Cance W.
Mod Pathol. 2005 Oct;18(10):1289-94.
PMID 15861214
Conditional deletion of the focal adhesion kinase FAK alters remodeling of the blood-brain barrier in glioma.
Lee J, Borboa AK, Chun HB, Baird A, Eliceiri BP.
Cancer Res. 2010 Dec 15;70(24):10131-40.
PMID 21159635
RNA interference-mediated silencing of focal adhesion kinase inhibits growth of human colon carcinoma xenograft in nude mice.
Lei K, Ye L, Yang Y, Wang GJ, Jiang QY, Jiang Y, Wei YQ, Deng HX.
J Biomed Nanotechnol. 2010 Jun;6(3):272-8.
PMID 21179944
Activation of FAK and Src are receptor-proximal events required for netrin signaling.
Li W, Lee J, Vikis HG, Lee SH, Liu G, Aurandt J, Shen TL, Fearon ER, Guan JL, Han M, Rao Y, Hong K, Guan KL.
Nat Neurosci. 2004 Nov;7(11):1213-21. Epub 2004 Oct 17.
PMID 15494734
Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis.
Lightfoot HM Jr, Lark A, Livasy CA, Moore DT, Cowan D, Dressler L, Craven RJ, Cance WG.
Breast Cancer Res Treat. 2004 Nov;88(2):109-16.
PMID 15564794
Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation.
Lim ST, Chen XL, Lim Y, Hanson DA, Vo TT, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D.
Mol Cell. 2008 Jan 18;29(1):9-22.
PMID 18206965
Extended survival of Pyk2 or FAK deficient orthotopic glioma xenografts.
Lipinski CA, Tran NL, Viso C, Kloss J, Yang Z, Berens ME, Loftus JC.
J Neurooncol. 2008 Nov;90(2):181-9. Epub 2008 Jul 22.
PMID 18648907
Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.
Liu G, Beggs H, Jurgensen C, Park HT, Tang H, Gorski J, Jones KR, Reichardt LF, Wu J, Rao Y.
Nat Neurosci. 2004 Nov;7(11):1222-32. Epub 2004 Oct 17.
PMID 15494732
Structural insight into the mechanisms of targeting and signaling of focal adhesion kinase.
Liu G, Guibao CD, Zheng J.
Mol Cell Biol. 2002 Apr;22(8):2751-60.
PMID 11909967
Focal adhesion kinase overexpression in endometrial neoplasia.
Livasy CA, Moore D, Cance WG, Lininger RA.
Appl Immunohistochem Mol Morphol. 2004 Dec;12(4):342-5.
PMID 15536334
Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells.
Luo M, Fan H, Nagy T, Wei H, Wang C, Liu S, Wicha MS, Guan JL.
Cancer Res. 2009 Jan 15;69(2):466-74.
PMID 19147559
Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130(Cas).
Ma A, Richardson A, Schaefer EM, Parsons JT.
Mol Biol Cell. 2001 Jan;12(1):1-12.
PMID 11160818
Inhibition of T24 human bladder carcinoma cell migration by RNA interference suppressing the expression of HD-PTP.
Mariotti M, Castiglioni S, Maier JA.
Cancer Lett. 2009 Jan 8;273(1):155-63. Epub 2008 Oct 2.
PMID 18835089
Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression.
McLean GW, Komiyama NH, Serrels B, Asano H, Reynolds L, Conti F, Hodivala-Dilke K, Metzger D, Chambon P, Grant SG, Frame MC.
Genes Dev. 2004 Dec 15;18(24):2998-3003.
PMID 15601818
Evaluation of FAK and Src expression in human benign and malignant thyroid lesions.
Michailidi C, Giaginis C, Stolakis V, Alexandrou P, Klijanienko J, Delladetsima I, Chatzizacharias N, Tsourouflis G, Theocharis S.
Pathol Oncol Res. 2010 Dec;16(4):497-507. Epub 2010 Apr 20.
PMID 20405349
Ligand-independent activation of c-Met by fibronectin and alpha(5)beta(1)-integrin regulates ovarian cancer invasion and metastasis.
Mitra AK, Sawada K, Tiwari P, Mui K, Gwin K, Lengyel E.
Oncogene. 2011 Mar 31;30(13):1566-76. Epub 2010 Nov 29.
PMID 21119598
Focal adhesion kinase: in command and control of cell motility.
Mitra SK, Hanson DA, Schlaepfer DD.
Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68. (REVIEW)
PMID 15688067
Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors.
Mitra SK, Mikolon D, Molina JE, Hsia DA, Hanson DA, Chi A, Lim ST, Bernard-Trifilo JA, Ilic D, Stupack DG, Cheresh DA, Schlaepfer DD.
Oncogene. 2006 Sep 28;25(44):5969-84. Epub 2006 May 8.
PMID 16682956
The expression and tyrosine phosphorylation of E-cadherin/catenin adhesion complex, and focal adhesion kinase in invasive cervical carcinomas.
Moon HS, Park WI, Choi EA, Chung HW, Kim SC.
Int J Gynecol Cancer. 2003 Sep-Oct;13(5):640-6.
PMID 14675348
Hyperglycemia-induced alteration of vascular smooth muscle phenotype.
Mori S, Takemoto M, Yokote K, Asaumi S, Saito Y.
J Diabetes Complications. 2002 Jan-Feb;16(1):65-8.
PMID 11872370
Glomerular overexpression and increased tyrosine phosphorylation of focal adhesion kinase p125FAK in lupus-prone MRL/MP-lpr/lpr mice.
Morino N, Matsumoto T, Ueki K, Mimura T, Hamasaki K, Kanda H, Naruse T, Yazaki Y, Nojima Y.
Immunology. 1999 Aug;97(4):634-40.
PMID 10457217
DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway.
Ocak S, Yamashita H, Udyavar AR, Miller AN, Gonzalez AL, Zou Y, Jiang A, Yi Y, Shyr Y, Estrada L, Quaranta V, Massion PP.
Oncogene. 2010 Dec 2;29(48):6331-42. Epub 2010 Aug 30.
PMID 20802517
Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas.
Oktay MH, Oktay K, Hamele-Bena D, Buyuk A, Koss LG.
Hum Pathol. 2003 Mar;34(3):240-5.
PMID 12673558
Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase.
Owen KA, Pixley FJ, Thomas KS, Vicente-Manzanares M, Ray BJ, Horwitz AF, Parsons JT, Beggs HE, Stanley ER, Bouton AH.
J Cell Biol. 2007 Dec 17;179(6):1275-87. Epub 2007 Dec 10.
PMID 18070912
Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors.
Owens LV, Xu L, Craven RJ, Dent GA, Weiner TM, Kornberg L, Liu ET, Cance WG.
Cancer Res. 1995 Jul 1;55(13):2752-5.
PMID 7796399
Focal adhesion kinase (FAK) expression in normal and neoplastic lymphoid tissues.
Ozkal S, Paterson JC, Tedoldi S, Hansmann ML, Kargi A, Manek S, Mason DY, Marafioti T.
Pathol Res Pract. 2009;205(11):781-8. Epub 2009 Aug 3.
PMID 19647948
Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling.
Palazzo AF, Eng CH, Schlaepfer DD, Marcantonio EE, Gundersen GG.
Science. 2004 Feb 6;303(5659):836-9.
PMID 14764879
Role of focal adhesion kinase Ser-732 phosphorylation in centrosome function during mitosis.
Park AY, Shen TL, Chien S, Guan JL.
J Biol Chem. 2009 Apr 3;284(14):9418-25. Epub 2009 Feb 6.
PMID 19201755
Focal adhesion kinase (FAK) gene amplification and its clinical implications in gastric cancer.
Park JH, Lee BL, Yoon J, Kim J, Kim MA, Yang HK, Kim WH.
Hum Pathol. 2010 Dec;41(12):1664-73. Epub 2010 Sep 24.
PMID 20869748
Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice.
Peng X, Kraus MS, Wei H, Shen TL, Pariaut R, Alcaraz A, Ji G, Cheng L, Yang Q, Kotlikoff MI, Chen J, Chien K, Gu H, Guan JL.
J Clin Invest. 2006 Jan;116(1):217-27. Epub 2005 Dec 22.
PMID 16374517
Cardiac developmental defects and eccentric right ventricular hypertrophy in cardiomyocyte focal adhesion kinase (FAK) conditional knockout mice.
Peng X, Wu X, Druso JE, Wei H, Park AY, Kraus MS, Alcaraz A, Chen J, Chien S, Cerione RA, Guan JL.
Proc Natl Acad Sci U S A. 2008 May 6;105(18):6638-43. Epub 2008 Apr 30.
PMID 18448675
Focal adhesion kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho.
Playford MP, Vadali K, Cai X, Burridge K, Schaller MD.
Exp Cell Res. 2008 Oct 15;314(17):3187-97. Epub 2008 Aug 23.
PMID 18773890
Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas.
Polte TR, Hanks SK.
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10678-82.
PMID 7479864
MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cells.
Ponnusamy MP, Lakshmanan I, Jain M, Das S, Chakraborty S, Dey P, Batra SK.
Oncogene. 2010 Oct 21;29(42):5741-54. Epub 2010 Aug 9.
PMID 20697346
Mammary epithelial-specific disruption of focal adhesion kinase retards tumor formation and metastasis in a transgenic mouse model of human breast cancer.
Provenzano PP, Inman DR, Eliceiri KW, Beggs HE, Keely PJ.
Am J Pathol. 2008 Nov;173(5):1551-65. Epub 2008 Oct 9.
PMID 18845837
Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling.
Pylayeva Y, Gillen KM, Gerald W, Beggs HE, Reichardt LF, Giancotti FG.
J Clin Invest. 2009 Feb;119(2):252-66. doi: 10.1172/JCI37160. Epub 2009 Jan 19.
PMID 19147981
Expression of focal adhesion kinase in acute myeloid leukemia is associated with enhanced blast migration, increased cellularity, and poor prognosis.
Recher C, Ysebaert L, Beyne-Rauzy O, Mansat-De Mas V, Ruidavets JB, Cariven P, Demur C, Payrastre B, Laurent G, Racaud-Sultan C.
Cancer Res. 2004 May 1;64(9):3191-7.
PMID 15126359
Focal adhesion kinase in netrin-1 signaling.
Ren XR, Ming GL, Xie Y, Hong Y, Sun DM, Zhao ZQ, Feng Z, Wang Q, Shim S, Chen ZF, Song HJ, Mei L, Xiong WC.
Nat Neurosci. 2004 Nov;7(11):1204-12. Epub 2004 Oct 17.
PMID 15494733
Expression of focal adhesion kinase in normal and pathologic human prostate tissues.
Rovin JD, Frierson HF Jr, Ledinh W, Parsons JT, Adams RB.
Prostate. 2002 Oct 1;53(2):124-32.
PMID 12242727
Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK.
Schaller MD, Borgman CA, Parsons JT.
Mol Cell Biol. 1993 Feb;13(2):785-91.
PMID 8423801
Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions.
Schaller MD.
J Cell Sci. 2010 Apr 1;123(Pt 7):1007-13. (REVIEW)
PMID 20332118
High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome.
Schmitz KJ, Grabellus F, Callies R, Otterbach F, Wohlschlaeger J, Levkau B, Kimmig R, Schmid KW, Baba HA.
Breast Cancer Res. 2005;7(2):R194-203. Epub 2005 Jan 7.
PMID 15743500
Targeting focal adhesion kinase with dominant-negative FRNK or Hsp90 inhibitor 17-DMAG suppresses tumor growth and metastasis of SiHa cervical xenografts.
Schwock J, Dhani N, Cao MP, Zheng J, Clarkson R, Radulovich N, Navab R, Horn LC, Hedley DW.
Cancer Res. 2009 Jun 1;69(11):4750-9. Epub 2009 May 19.
PMID 19458065
Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues.
Shahrara S, Castro-Rueda HP, Haines GK, Koch AE.
Arthritis Res Ther. 2007;9(5):R112.
PMID 17963503
Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis.
Shen TL, Park AY, Alcaraz A, Peng X, Jang I, Koni P, Flavell RA, Gu H, Guan JL.
J Cell Biol. 2005 Jun 20;169(6):941-52.
PMID 15967814
A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth.
Shi Q, Hjelmeland AB, Keir ST, Song L, Wickman S, Jackson D, Ohmori O, Bigner DD, Friedman HS, Rich JN.
Mol Carcinog. 2007 Jun;46(6):488-96.
PMID 17219439
[Tyrosine phosphorylation of focal adhesion kinase (p125FAK) and paxillin in glomeruli from diabetic rats].
Shikano T, Haneda M, Togawa M, Kikkawa R.
Nippon Jinzo Gakkai Shi. 1996 Feb;38(2):57-64.
PMID 8717307
FAK integrates growth-factor and integrin signals to promote cell migration.
Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH, Schlaepfer DD.
Nat Cell Biol. 2000 May;2(5):249-56.
PMID 10806474
Alphavbeta3/alphavbeta5 integrins-FAK-RhoB: a novel pathway for hypoxia regulation in glioblastoma.
Skuli N, Monferran S, Delmas C, Favre G, Bonnet J, Toulas C, Cohen-Jonathan Moyal E.
Cancer Res. 2009 Apr 15;69(8):3308-16. Epub 2009 Apr 7.
PMID 19351861
Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype.
Smit DJ, Gardiner BB, Sturm RA.
Int J Cancer. 2007 Dec 15;121(12):2653-60.
PMID 17724718
Effect of focal adhesion kinase (FAK) downregulation with FAK antisense oligonucleotides and 5-fluorouracil on the viability of melanoma cell lines.
Smith CS, Golubovskaya VM, Peck E, Xu LH, Monia BP, Yang X, Cance WG.
Melanoma Res. 2005 Oct;15(5):357-62.
PMID 16179862
Anti-apoptotic role of focal adhesion kinase (FAK). Induction of inhibitor-of-apoptosis proteins and apoptosis suppression by the overexpression of FAK in a human leukemic cell line, HL-60.
Sonoda Y, Matsumoto Y, Funakoshi M, Yamamoto D, Hanks SK, Kasahara T.
J Biol Chem. 2000 May 26;275(21):16309-15.
PMID 10821872
Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis.
Sood AK, Armaiz-Pena GN, Halder J, Nick AM, Stone RL, Hu W, Carroll AR, Spannuth WA, Deavers MT, Allen JK, Han LY, Kamat AA, Shahzad MM, McIntyre BW, Diaz-Montero CM, Jennings NB, Lin YG, Merritt WM, DeGeest K, Vivas-Mejia PE, Lopez-Berestein G, Schaller MD, Cole SW, Lutgendorf SK.
J Clin Invest. 2010 May 3;120(5):1515-23. doi: 10.1172/JCI40802. Epub 2010 Apr 12.
PMID 20389021
Biological significance of focal adhesion kinase in ovarian cancer: role in migration and invasion.
Sood AK, Coffin JE, Schneider GB, Fletcher MS, DeYoung BR, Gruman LM, Gershenson DM, Schaller MD, Hendrix MJ.
Am J Pathol. 2004 Oct;165(4):1087-95.
PMID 15466376
Doxycycline inhibits the adhesion and migration of melanoma cells by inhibiting the expression and phosphorylation of focal adhesion kinase (FAK).
Sun T, Zhao N, Ni CS, Zhao XL, Zhang WZ, Su X, Zhang DF, Gu Q, Sun BC.
Cancer Lett. 2009 Nov 28;285(2):141-50. Epub 2009 May 30.
PMID 19482420
Focal adhesion kinase is required for the spatial organization of the leading edge in migrating cells.
Tilghman RW, Slack-Davis JK, Sergina N, Martin KH, Iwanicki M, Hershey ED, Beggs HE, Reichardt LF, Parsons JT.
J Cell Sci. 2005 Jun 15;118(Pt 12):2613-23. Epub 2005 May 24.
PMID 15914540
Focal adhesion kinase (pp125FAK) expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma.
Tremblay L, Hauck W, Aprikian AG, Begin LR, Chapdelaine A, Chevalier S.
Int J Cancer. 1996 Oct 9;68(2):164-71.
PMID 8900422
CAV1 inhibits metastatic potential in melanomas through suppression of the integrin/Src/FAK signaling pathway.
Trimmer C, Whitaker-Menezes D, Bonuccelli G, Milliman JN, Daumer KM, Aplin AE, Pestell RG, Sotgia F, Lisanti MP, Capozza F.
Cancer Res. 2010 Oct 1;70(19):7489-99. Epub 2010 Aug 13.
PMID 20709760
Focal adhesion kinase: an essential kinase in the regulation of cardiovascular functions.
Vadali K, Cai X, Schaller MD.
IUBMB Life. 2007 Nov;59(11):709-16. (REVIEW)
PMID 17968709
Acquisition of chemoresistance following discontinuous exposures to cisplatin is associated in ovarian carcinoma cells with progressive alteration of FAK, ERK and p38 activation in response to treatment.
Villedieu M, Deslandes E, Duval M, Heron JF, Gauduchon P, Poulain L.
Gynecol Oncol. 2006 Jun;101(3):507-19. Epub 2006 Jan 4.
PMID 16387351
Expression of FAK and PTEN in bronchioloalveolar carcinoma and lung adenocarcinoma.
Wang C, Yang R, Yue D, Zhang Z.
Lung. 2009 Mar-Apr;187(2):104-9. Epub 2009 Feb 26.
PMID 19242756
RNA interference-mediated silencing of focal adhesion kinase inhibits growth of human malignant glioma xenograft in nude mice.
Wang GJ, Ma YP, Yang Y, Zhang N, Wang W, Liu SY, Chen LJ, Jiang Y, Zhao X, Wei YQ, Deng HX.
Cell Biol Int. 2011 Jan 20. [Epub ahead of print]
PMID 21247411
Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors.
Weiner TM, Liu ET, Craven RJ, Cance WG.
Ann Surg Oncol. 1994 Jan;1(1):18-27.
PMID 7834423
Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration.
Xie Z, Sanada K, Samuels BA, Shih H, Tsai LH.
Cell. 2003 Aug 22;114(4):469-82.
PMID 12941275
Heparin-binding epidermal growth factor-like growth factor promotes transcoelomic metastasis in ovarian cancer through epithelial-mesenchymal transition.
Yagi H, Yotsumoto F, Miyamoto S.
Mol Cancer Ther. 2008 Oct;7(10):3441-51.
PMID 18852147
Inhibition of cell motility by troglitazone in human ovarian carcinoma cell line.
Yang YC, Ho TC, Chen SL, Lai HY, Wu JY, Tsao YP.
BMC Cancer. 2007 Nov 20;7:216.
PMID 18021457
Roles played by a subset of integrin signaling molecules in cadherin-based cell-cell adhesion.
Yano H, Mazaki Y, Kurokawa K, Hanks SK, Matsuda M, Sabe H.
J Cell Biol. 2004 Jul 19;166(2):283-95.
PMID 15263022
Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer.
Yom CK, Noh DY, Kim WH, Kim HS.
Breast Cancer Res Treat. 2010 Sep 3. [Epub ahead of print]
PMID 20814816
Mesenchymal mode of migration participates in pulmonary metastasis of mouse osteosarcoma LM8.
Yui Y, Itoh K, Yoshioka K, Naka N, Watanabe M, Hiraumi Y, Matsubara H, Watanabe K, Sano K, Nakahata T, Adachi S.
Clin Exp Metastasis. 2010 Dec;27(8):619-30. Epub 2010 Sep 26.
PMID 20872237
PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration.
Zeng L, Si X, Yu WP, Le HT, Ng KP, Teng RM, Ryan K, Wang DZ, Ponniah S, Pallen CJ.
J Cell Biol. 2003 Jan 6;160(1):137-46. Epub 2003 Jan 6.
PMID 12515828
Focal adhesion kinase promotes phospholipase C-gamma1 activity.
Zhang X, Chattopadhyay A, Ji QS, Owen JD, Ruest PJ, Carpenter G, Hanks SK.
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9021-6.
PMID 10430888
Prostatic carcinoma cell migration via alpha(v)beta3 integrin is modulated by a focal adhesion kinase pathway.
Zheng DQ, Woodard AS, Fornaro M, Tallini G, Languino LR.
Cancer Res. 1999 Apr 1;59(7):1655-64.
PMID 10197643
Combined expression of the non-receptor protein tyrosine kinases FAK and Src in primary colorectal cancer is associated with tumor recurrence and metastasis formation.
de Heer P, Koudijs MM, van de Velde CJ, Aalbers RI, Tollenaar RA, Putter H, Morreau J, van de Water B, Kuppen PJ.
Eur J Surg Oncol. 2008 Nov;34(11):1253-61. Epub 2008 Jun 16.
PMID 18556171
Complete focal adhesion kinase deficiency in the mammary gland causes ductal dilation and aberrant branching morphogenesis through defects in Rho kinase-dependent cell contractility.
van Miltenburg MH, Lalai R, de Bont H, van Waaij E, Beggs H, Danen EH, van de Water B.
FASEB J. 2009 Oct;23(10):3482-93. Epub 2009 Jul 7.
PMID 19584305


This paper should be referenced as such :
Schwock, J ; Dhani, N
PTK2 (PTK2 protein tyrosine kinase 2)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(10):854-866.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Chronic myelogenous leukaemia (CML)

External links


HGNC (Hugo)PTK2   9611
Entrez_Gene (NCBI)PTK2    protein tyrosine kinase 2
AliasesFADK; FADK; FAK; FAK1; 
FRNK; PPP1R71; p125FAK; pp125FAK
GeneCards (Weizmann)PTK2
Ensembl hg19 (Hinxton)ENSG00000169398 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000169398 [Gene_View]  ENSG00000169398 [Sequence]  chr8:140657900-141001282 [Contig_View]  PTK2 [Vega]
ICGC DataPortalENSG00000169398
TCGA cBioPortalPTK2
AceView (NCBI)PTK2
Genatlas (Paris)PTK2
SOURCE (Princeton)PTK2
Genetics Home Reference (NIH)PTK2
Genomic and cartography
GoldenPath hg38 (UCSC)PTK2  -     chr8:140657900-141001282 -  8q24.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PTK2  -     8q24.3   [Description]    (hg19-Feb_2009)
GoldenPathPTK2 - 8q24.3 [CytoView hg19]  PTK2 - 8q24.3 [CytoView hg38]
Genome Data Viewer NCBIPTK2 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB209071 AB209083 AK055139 AK094999 AK124810
RefSeq transcript (Entrez)NM_001199649 NM_001316342 NM_001352694 NM_001352695 NM_001352696 NM_001352697 NM_001352698 NM_001352699 NM_001352700 NM_001352701 NM_001352702 NM_001352703 NM_001352704 NM_001352705 NM_001352706 NM_001352707 NM_001352708 NM_001352709 NM_001352710 NM_001352711 NM_001352712 NM_001352713 NM_001352714 NM_001352715 NM_001352716 NM_001352717 NM_001352718 NM_001352719 NM_001352720 NM_001352721 NM_001352722 NM_001352723 NM_001352724 NM_001352725 NM_001352726 NM_001352727 NM_001352728 NM_001352729 NM_001352730 NM_001352731 NM_001352732 NM_001352733 NM_001352734 NM_001352735 NM_001352736 NM_001352737 NM_001352738 NM_001352739 NM_001352740 NM_001352741 NM_001352742 NM_001352743 NM_001352744 NM_001352745 NM_001352746 NM_001352747 NM_001352748 NM_001352749 NM_001352750 NM_001352751 NM_001352752 NM_001387584 NM_001387585 NM_001387586 NM_001387587 NM_001387588 NM_001387589 NM_001387590 NM_001387591 NM_001387592 NM_001387603 NM_001387604 NM_001387605 NM_001387606 NM_001387607 NM_001387608 NM_001387609 NM_001387610 NM_001387611 NM_001387612 NM_001387613 NM_001387614 NM_001387615 NM_001387616 NM_001387617 NM_001387618 NM_001387619 NM_001387620 NM_001387621 NM_001387622 NM_001387623 NM_001387624 NM_001387625 NM_001387627 NM_001387628 NM_001387629 NM_001387630 NM_001387631 NM_001387632 NM_001387633 NM_001387634 NM_001387635 NM_001387636 NM_001387637 NM_001387638 NM_001387639 NM_001387640 NM_001387641 NM_001387642 NM_001387643 NM_001387644 NM_001387645 NM_001387646 NM_001387647 NM_001387648 NM_001387649 NM_001387650 NM_001387651 NM_001387652 NM_001387653 NM_001387654 NM_001387655 NM_001387656 NM_001387657 NM_001387658 NM_001387659 NM_001387660 NM_001387661 NM_001387662 NM_005607 NM_153831
Consensus coding sequences : CCDS (NCBI)PTK2
Gene ExpressionPTK2 [ NCBI-GEO ]   PTK2 [ EBI - ARRAY_EXPRESS ]   PTK2 [ SEEK ]   PTK2 [ MEM ]
Gene Expression Viewer (FireBrowse)PTK2 [ Firebrowse - Broad ]
GenevisibleExpression of PTK2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5747
GTEX Portal (Tissue expression)PTK2
Human Protein AtlasENSG00000169398-PTK2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ05397   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ05397  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ05397
Catalytic activity : Enzyme2.7.10.2 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)FERM_2 (PS00661)    FERM_3 (PS50057)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)   
Domains : Interpro (EBI)Band_41_domain    FADK_N    FAK1/PYK2_FERM_C    FERM/acyl-CoA-bd_prot_sf    FERM_2    FERM_central    FERM_domain    Focal_adhe_kin_target_dom_sf    Focal_adhesion_kin_target_dom    Kinase-like_dom_sf    PH-like_dom_sf    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kinase_AS    Tyr_kinase_cat_dom    Ubiquitin-like_domsf   
Domain families : Pfam (Sanger)FERM_M (PF00373)    FERM_N_2 (PF18038)    Focal_AT (PF03623)    PK_Tyr_Ser-Thr (PF07714)   
Domain families : Pfam (NCBI)pfam00373    pfam18038    pfam03623    pfam07714   
Domain families : Smart (EMBL)B41 (SM00295)  TyrKc (SM00219)  
Conserved Domain (NCBI)PTK2
PDB (RSDB)1K04    1K05    1MP8    1OW6    1OW7    1OW8    2ETM    2IJM    3B71    3BZ3    3PXK    3S9O    4EBV    4EBW    4GU6    4GU9    4I4E    4I4F    4K8A    4K9Y    4KAB    4KAO    4NY0    4Q9S    6I8Z    6LES    6PW8   
PDB Europe1K04    1K05    1MP8    1OW6    1OW7    1OW8    2ETM    2IJM    3B71    3BZ3    3PXK    3S9O    4EBV    4EBW    4GU6    4GU9    4I4E    4I4F    4K8A    4K9Y    4KAB    4KAO    4NY0    4Q9S    6I8Z    6LES    6PW8   
PDB (PDBSum)1K04    1K05    1MP8    1OW6    1OW7    1OW8    2ETM    2IJM    3B71    3BZ3    3PXK    3S9O    4EBV    4EBW    4GU6    4GU9    4I4E    4I4F    4K8A    4K9Y    4KAB    4KAO    4NY0    4Q9S    6I8Z    6LES    6PW8   
PDB (IMB)1K04    1K05    1MP8    1OW6    1OW7    1OW8    2ETM    2IJM    3B71    3BZ3    3PXK    3S9O    4EBV    4EBW    4GU6    4GU9    4I4E    4I4F    4K8A    4K9Y    4KAB    4KAO    4NY0    4Q9S    6I8Z    6LES    6PW8   
Structural Biology KnowledgeBase1K04    1K05    1MP8    1OW6    1OW7    1OW8    2ETM    2IJM    3B71    3BZ3    3PXK    3S9O    4EBV    4EBW    4GU6    4GU9    4I4E    4I4F    4K8A    4K9Y    4KAB    4KAO    4NY0    4Q9S    6I8Z    6LES    6PW8   
SCOP (Structural Classification of Proteins)1K04    1K05    1MP8    1OW6    1OW7    1OW8    2ETM    2IJM    3B71    3BZ3    3PXK    3S9O    4EBV    4EBW    4GU6    4GU9    4I4E    4I4F    4K8A    4K9Y    4KAB    4KAO    4NY0    4Q9S    6I8Z    6LES    6PW8   
CATH (Classification of proteins structures)1K04    1K05    1MP8    1OW6    1OW7    1OW8    2ETM    2IJM    3B71    3BZ3    3PXK    3S9O    4EBV    4EBW    4GU6    4GU9    4I4E    4I4F    4K8A    4K9Y    4KAB    4KAO    4NY0    4Q9S    6I8Z    6LES    6PW8   
AlphaFold pdb e-kbQ05397   
Human Protein Atlas [tissue]ENSG00000169398-PTK2 [tissue]
Protein Interaction databases
IntAct (EBI)Q05397
Ontologies - Pathways
Ontology : AmiGOMAPK cascade  angiogenesis  angiogenesis  stress fiber  placenta development  regulation of protein phosphorylation  positive regulation of protein phosphorylation  heart morphogenesis  actin binding  protein tyrosine kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  signaling receptor binding  integrin binding  protein binding  ATP binding  nucleus  cytoplasm  cytosol  cytosol  cytoskeleton  plasma membrane  focal adhesion  focal adhesion  cell cortex  transmembrane receptor protein tyrosine kinase signaling pathway  signal complex assembly  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  integrin-mediated signaling pathway  integrin-mediated signaling pathway  integrin-mediated signaling pathway  axon guidance  positive regulation of cell population proliferation  regulation of cell shape  JUN kinase binding  regulation of endothelial cell migration  regulation of epithelial cell migration  positive regulation of macrophage chemotaxis  positive regulation of fibroblast migration  positive regulation of phosphatidylinositol 3-kinase signaling  cell migration  peptidyl-tyrosine phosphorylation  protein kinase binding  protein phosphatase binding  negative regulation of cell-cell adhesion  establishment of cell polarity  cell differentiation  regulation of cell adhesion  positive regulation of cell migration  extrinsic component of cytoplasmic side of plasma membrane  regulation of cell adhesion mediated by integrin  detection of muscle stretch  ciliary basal body  netrin-activated signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  regulation of cell population proliferation  SH2 domain binding  negative regulation of apoptotic process  regulation of GTPase activity  dendritic spine  intracellular membrane-bounded organelle  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  regulation of osteoblast differentiation  positive regulation of protein kinase activity  protein autophosphorylation  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  ephrin receptor signaling pathway  cell motility  regulation of cytoskeleton organization  regulation of focal adhesion assembly  regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  growth hormone receptor signaling pathway  positive regulation of wound healing  positive regulation of macrophage proliferation  regulation of substrate adhesion-dependent cell spreading  positive regulation of ubiquitin-dependent protein catabolic process  negative regulation of anoikis  
Ontology : EGO-EBIMAPK cascade  angiogenesis  angiogenesis  stress fiber  placenta development  regulation of protein phosphorylation  positive regulation of protein phosphorylation  heart morphogenesis  actin binding  protein tyrosine kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  non-membrane spanning protein tyrosine kinase activity  signaling receptor binding  integrin binding  protein binding  ATP binding  nucleus  cytoplasm  cytosol  cytosol  cytoskeleton  plasma membrane  focal adhesion  focal adhesion  cell cortex  transmembrane receptor protein tyrosine kinase signaling pathway  signal complex assembly  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  integrin-mediated signaling pathway  integrin-mediated signaling pathway  integrin-mediated signaling pathway  axon guidance  positive regulation of cell population proliferation  regulation of cell shape  JUN kinase binding  regulation of endothelial cell migration  regulation of epithelial cell migration  positive regulation of macrophage chemotaxis  positive regulation of fibroblast migration  positive regulation of phosphatidylinositol 3-kinase signaling  cell migration  peptidyl-tyrosine phosphorylation  protein kinase binding  protein phosphatase binding  negative regulation of cell-cell adhesion  establishment of cell polarity  cell differentiation  regulation of cell adhesion  positive regulation of cell migration  extrinsic component of cytoplasmic side of plasma membrane  regulation of cell adhesion mediated by integrin  detection of muscle stretch  ciliary basal body  netrin-activated signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  regulation of cell population proliferation  SH2 domain binding  negative regulation of apoptotic process  regulation of GTPase activity  dendritic spine  intracellular membrane-bounded organelle  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  regulation of osteoblast differentiation  positive regulation of protein kinase activity  protein autophosphorylation  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  ephrin receptor signaling pathway  cell motility  regulation of cytoskeleton organization  regulation of focal adhesion assembly  regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  growth hormone receptor signaling pathway  positive regulation of wound healing  positive regulation of macrophage proliferation  regulation of substrate adhesion-dependent cell spreading  positive regulation of ubiquitin-dependent protein catabolic process  negative regulation of anoikis  
Pathways : KEGGErbB signaling pathway    Chemokine signaling pathway    PI3K-Akt signaling pathway    Axon guidance    VEGF signaling pathway    Focal adhesion    Leukocyte transendothelial migration    Regulation of actin cytoskeleton    Bacterial invasion of epithelial cells    Amoebiasis    Pathways in cancer    Transcriptional misregulation in cancer    Proteoglycans in cancer    Small cell lung cancer   
REACTOMEQ05397 [protein]
REACTOME PathwaysR-HSA-9634638 [pathway]   
NDEx NetworkPTK2
Atlas of Cancer Signalling NetworkPTK2
Wikipedia pathwaysPTK2
Orthology - Evolution
GeneTree (enSembl)ENSG00000169398
Phylogenetic Trees/Animal Genes : TreeFamPTK2
Homologs : HomoloGenePTK2
Homology/Alignments : Family Browser (UCSC)PTK2
Gene fusions - Rearrangements
Fusion : MitelmanAGO2::PTK2 [8q24.3/8q24.3]  
Fusion : MitelmanPTDSS1::PTK2 [8q22.1/8q24.3]  
Fusion : MitelmanPTK2::ANKRD11 [8q24.3/16q24.3]  
Fusion : MitelmanPTK2::CACNG8 [8q24.3/19q13.42]  
Fusion : MitelmanPTK2::NCR3 [8q24.3/6p21.33]  
Fusion : MitelmanPTK2::PKHD1L1 [8q24.3/8q23.1]  
Fusion : MitelmanPTK2::PPP2R5E [8q24.3/14q23.2]  
Fusion : MitelmanPTK2::RNF139 [8q24.3/8q24.13]  
Fusion : MitelmanPTK2::SLC45A4 [8q24.3/8q24.3]  
Fusion : MitelmanPTK2::TRAPPC9 [8q24.3/8q24.3]  
Fusion : MitelmanPTK2::UBE2H [8q24.3/7q32.2]  
Fusion : MitelmanPTK2::UGT2A3 [8q24.3/4q13.2]  
Fusion : MitelmanSP3::PTK2 [2q31.1/8q24.3]  
Fusion : MitelmanTRAPPC9::PTK2 [8q24.3/8q24.3]  
Fusion : FusionGDB2.7.10.1   
Fusion : QuiverPTK2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPTK2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PTK2
Exome Variant ServerPTK2
GNOMAD BrowserENSG00000169398
Varsome BrowserPTK2
ACMGPTK2 variants
Genomic Variants (DGV)PTK2 [DGVbeta]
DECIPHERPTK2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPTK2 
ICGC Data PortalPTK2 
TCGA Data PortalPTK2 
Broad Tumor PortalPTK2
OASIS PortalPTK2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPTK2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPTK2
Mutations and Diseases : HGMDPTK2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)PTK2
DoCM (Curated mutations)PTK2
CIViC (Clinical Interpretations of Variants in Cancer)PTK2
NCG (London)PTK2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PTK2
NextProtQ05397 [Medical]
Target ValidationPTK2
Huge Navigator PTK2 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDPTK2
Pharm GKB GenePA33955
Clinical trialPTK2
DataMed IndexPTK2
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:26:04 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us