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BCAR1 (breast cancer anti-estrogen resistance 1)

Written2011-12Allison Berrier
Department of Oral, Craniofacial Biology, LSUHSC-NO School of Dentistry, 1100 Florida Avenue, Clinical Bldg, Room 8301, New Orleans, LA 70119, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesbreast cancer anti-estrogen resistance 1
Alias_symbol (synonym)P130Cas
Crkas
CAS
CASS1
Other aliasCAS1
CRKAS
FLJ12176
FLJ45059
HGNC (Hugo) BCAR1
LocusID (NCBI) 9564
Atlas_Id 761
Location 16q23.1  [Link to chromosome band 16q23]
Location_base_pair Starts at 75228187 and ends at 75251656 bp from pter ( according to hg19-Feb_2009)  [Mapping BCAR1.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)
BCAR1 (16q23.1) / BCAR1 (16q23.1)LDHB (12p12.1) / BCAR1 (16q23.1)RBM6 (3p21.31) / BCAR1 (16q23.1)

DNA/RNA

 
  Figure 1.

Protein

Note BCAR1 isoforms
Isoform 1: 916 aa, calc MW= 97,7 kDa. Isoform 2: 888 aa, (alternate 5' sequence compared to variant 1) calc MW= 95,1 kDa. Isoform 3: 888 aa, (alternate 5' sequence compared to variant 1) calc MW= 95,3 kDa. Isoform 4: 888 aa, (alternate 5' sequence and alternate splice site in the substrate domain compared to variant 1 resulting in a different N-terminus and additional segment in the middle region compared to isoform 1) calc MW= 95,3 kDa. Isoform 5: 870 aa, (lacks an exon in the 5' region, alternate AUG start codon, has a different N-terminus compared to isoform 1) calc MW= 93,16 kDa. Isoform 6: 870 aa, (different N-terminus compared to isoform 1) calc MW= 93,2 kDa. Isoform 7, 868 aa (shorter, alternate 5' sequence, different N-terminus compared to isoform 1) calc MW= 93 kDa. Isoform 8, 722 aa, (alternate internal sequence compared to isoform 1, different N-terminus compared to isoform 1) calc MW= 77,6 kDa. Isoform 9: 660 aa, (shorter alternate 5' sequence, different N-terminus compared to isoform 1) calc MW= 70,7 kDa.

BCAR proteins migrate during SDS-PAGE electrophoresis at a significantly higher molecular weight than predicted from sequence analysis perhaps due to the extensive phosphorylation of BCAR proteins. Calculated MW 93,2 kDa, SDS-PAGE observed MW 130 kDa. Potential sites of human BCAR1 phosphorylation (PhosphoSitePlus): tyrosine residues aa 12, 128, 165, 192, 222, 224, 234, 249, 267, 287, 306, 327, 362, 372, 387, 410, 653, 664, 666; serine residues aa 134, 139, 292, 437, 639; and threonine residues aa 269, 326, 385. Inducers of BCAR1 phosphorylation include cell matrix adhesion, extracellular matrix rigidity, growth factors, hormones and progression through the cell cycle. Phosphorylation of BCAR1 regulates BCAR1 dependent activities through altering protein interactions, protein localization and signaling cascades (Tikhmyanova et al., 2010).

 
  Figure 2. Schematic diagram containing BCAR1 protein domains.
Description BCAR1 domains as described in Tikhmyanova et al., 2010 are shown in the schematic diagram in figure 2. The amino terminal 1-65 aa contain the Src homology 3 domain (SH3) domain that binds proline-rich PxxP ligands. The adjacent region 66-447 aa contains the substrate domain (SD) comprised of 15 YxxP motifs that when phosphorylated by tyrosine kinases provides canonical binding sites for proteins containing SH2 domains such as Crk, mechanical forces and stretching of SD may induce conformational changes that allows phosphorylation by kinases and this stretching may promote protein-protein interactions in this domain (Sawada et al., 2006). The serine rich domain within 448-610 aa (serine rich protein interaction domain) contains a four-helix bundle that functions as a scaffold for BCAR1 binding proteins such as Grb2 and 14-3-3 (Nasertorabi et al., 2004; Briknarová et al., 2005). The C-terminal domain of 746-870 aa has a potential FAT (focal adhesion targeting) domain and a helix-loop-helix domain with homology to the transcription factor Id. This region contains the YDYVHL motif that is phosphorylated during cell adhesion.

BCAR1 interacting proteins (BioGRID)
CRKII, p60-Src, PTPN12, PTK2 (FAK), RapGEF1 (C3G), NPHP1, PTPN1 (PTP1B), FES, SHIP2 (INPPL1), ARHGAP32 (p250GAP), Pyk2 (PTK2B), Fyn, CRKL, YWHAZ, SrcIN1 (SNIP), p85-alpha (PI3KR1), c-ABL (bcr/abl), Lyn, Grb2, Dock1, paxillin, TRIP6, SH-PTP2, ID2A, UHRF2, NEDD9, NCK1, VCL, SAP1, Zyxin, BCAR3 (AND-34), CD2AP, LCK, SFN, SH2D3C, JNK/SAPK1, SH3KBP1, tensin 1 (TNS1), HCK, EFS, E2F2, VPS11, HspA5, TUBA1A, GADD34, p140Cap, BCAR1 (p130CAS), PTP-PEST, CIZ, Aurora-A, 14-3-3, CHAT-H, AIP4, APC/C and CDH1.

Expression BCAR1 is ubiquitously expressed and is reportedly detectable in all phases of the cell cycle. In lymphoid development, BCAR is expressed at higher levels in differentiated cells compared to precursors. Barrett's esophagus cancer cell line compared to normal tissue 2,51 increase in BCAR1 expression (Oncomine). Colorectal cancer Ramaswamy multi-cancer there is a 4,2 fold increase in BCAR1 expression compared to other cancers (Oncomine). Gastric cancer cell line Gyorffy cell line 2 there is a 5,0 fold reduction in BCAR 1 expression (Oncomine). In lymphomas, BCAR1 expression is reduced 2,5 fold (Oncomine).
Localisation Cytoplasm, ruffles, cell junctions (Donaldson et al., 2000), nucleus (Kim et al., 2004) and focal adhesions (Nakamoto et al., 1997; Volberg et al., 1995; Winograd-Katz et al., 2009).
Function BCAR1 regulates numerous cellular processes such as invasion, migration, transformation, survival and drug resistance (Di Stefano et al., 2011; Brábek et al., 2004; Brábek et al., 2005) (summarized in figure 3). BCAR1 lacks intrinsic enzymatic activity, yet it is a substrate for several kinases including the Src tyrosine kinase. The original name for BCAR1 was p130CAS abbreviated from Crk-associated substrate because it was first identified as a tyrosine phosphorylated protein in cells transformed by v-src and v-crk oncogenes. BCAR1 regulates cellular behavior by controlling signaling cascades and the dynamic localization of multi-protein complexes. The BCAR1 phosphorylation state is regulated during the cell cycle. During the exit of G2, BCAR1 serine and threonine phosphorylation levels increase and these events disrupt the interactions of BCAR1 with Src and FAK and thus dissociates this complex and contributes to the disassembly of focal adhesions allowing cells to loosen matrix adhesions and thus permitting cell rounding in mitosis. The subsequent reformation of matrix adhesions promotes progression through the cell cycle from mitosis to G1 (Pugacheva et al., 2006).
 
  Figure 3. Extracellular cues that control CAR1 phosphorylation and cellular processes that are regulated by BCAR1.
Homology There is a family containing four proteins related to BCAR1 (breast cancer resistance) that possess names related to the prior nomenclature for BCAR1 homologs in the rat and mouse. The non-human homologs of BCAR1 were named CAS for Crk-associated substrate. This family of proteins includes the protein EFS (embryonal Fyn-associated substrate) (CAS3, CASS3, EFS1, EFS2, HEFS, SIN) identified because of interactions with the Src-family kinases Fyn and Yes and maps to chromosome 14q11.2-q12. A third family member is HEF1 (human enhancer of filamentation 1 known as CASL, CAS-L, NEDD9, CAS2 and CASS2) that maps to chromosome 6p25-p24 and was isolated as a human gene that promotes filamentous growth in yeast. This screen was performed to identify regulators of the cell cycle and polarity. It was also identified as a protein that is tyrosine phosphorylated after clustering integrin β1 in T-lymphocytes. NEDD9 (neural precursor cell expressed, developmentally down-regulated 9) is a gene restricted in expression to early embryonic, but not adult mouse brain. The fourth family member is CASS4 ((HEF-EFS-P130CAS-like)/CAS4) that maps to chromosome 20q13.2-q13.31 and is the newest member of the family that was identified by genomic and transcript homology and demonstrated to function similarly to other BCAR family members. These 4 proteins are conserved from jawed vertebrates through mammals. One BCAR member is found in lower vertebrates and insects. However, no BCAR family member is detectable in C. elegans, S. cerevisiae and other lower eukaryotes.

Mutations

Somatic Catalogue of somatic mutations in cancer: there are currently 10 known somatic mutations in BCAR1. Proceeding from the N-terminus to the C-Terminus of BCAR1, aa 118 proline (identified in the central nervous system), 185 alanine (identified in the central nervous system), 407 threonine (identified in breast tissue), 430 serine (upper aerodigestive tract), 583 serine (identified in prostate tissue), 592 histidine (identified in liver), 708 lysine (identified in the central nervous system), 759 threonine (identified in central nervous system), 780 valine (identified in central nervous system), 795 isoleucine (identified in upper aerodigestive tract). Mutations at aa 118 and 185 are in the substrate domain, 407 and 430 are amino-terminal to the 4 helical bundle, 583 and 592 are in the 4-helix bundle, whereas 759, 780 and 795 localize to the C-terminal domain.

Implicated in

Note
  
Entity Various cancers
Note Overexpression of BCAR1 is linked to poor prognosis and increased cancer metastasis in many cancers. BCAR1 can be upregulated by gene amplification, transcriptional upregulation and changes in protein stability. Hyperphosphorylation of BCAR1 drives cell migration, invasion, cell survival and drug resistance.
  
  
Entity Breast cancer
Prognosis In breast cancers that express high levels of BCAR1, the cancer is more likely to relapse and the tumors frequently have an intrinsic reduced response to tamoxifen (van der Flier et al., 2000; Dorssers et al., 2004).
Oncogenesis Elevated BCAR levels in breast cancers correlates with increased expression of HER2/neu and enhanced cell proliferation (Cabodi et al., 2006; Cabodi et al., 2010). BCAR1 overexpression in breast cancer cells is linked to resistance to the cytotoxic agent Adriamycin (Ta et al., 2008). BCAR1 overexpression is sufficient to induce hyperplasia in the mammary pad during development and pregnancy.
  
  
Entity Prostate cancer
Oncogenesis In prostate cancer, BCAR1 expression is higher compared to control tissue and expression of BCAR1 in prostate cancer correlates with elevated EGFR expression levels (Fromont et al., 2007; Fromont et al., 2011; Cabodi et al., 2010).
  
  
Entity Hepatocellular carcinoma
Prognosis In hepatocellular carcinoma, tumor invasion and poor prognosis correlate with overexpression of BCAR1 and reductions in E-cadherin and β-catenin levels (Guo et al., 2008).
  
  
Entity Nasal polyps
Oncogenesis Nasal polyps can express high levels of BCAR1 (Zhang et al., 2003).
  
  
Entity Colorectal cancer
Oncogenesis Celecoxib cytotoxicity in colorectal cancer is linked to cleavage of BCAR1 and apoptosis. Overexpression of BCAR1 in colorectal cancer cell lines is linked to resistance to celecoxib (Casanova et al., 2006; Weyant et al., 2000).
  
  
Entity Non-small-cell lung cancer (NSCLC)
Oncogenesis BCAR1 is not detected in normal lung tissue, however in non-small-cell lung cancer and tuberculosis and other pulmonary disorders elevated levels of BCAR1 are observed in both the diseased tissue and elevated levels are noted in serum (Deng et al., 2011). In patients with NSCLC the serum levels of BCAR1 proportionally increase with the progression of tumor stage. Interestingly, in patients with elevated serum BCAR1 levels, the serum levels of BCAR1 diminish after removal of the pulmonary lesion or tumor.
  
  
Entity Ovarian cancer
Prognosis In ovarian cancer, an increase in BCAR1 expression correlates with poor 5 year survival rates and reductions in BCAR1 expression result in reduced tumor growth following docetaxel chemotherapy (Nick et al., 2011).
  
  
Entity Oral cancer
Oncogenesis In oral cancers elevated levels of UPAR are indicative of more invasive tumors and enhanced lymph node metastasis. The levels of UPAR in oral cancer correlate with the levels of BCAR1 (Shi et al., 2011).
  
  
Entity Anaplastic large-cell lymphomas
Oncogenesis In anaplastic large-cell lymphomas, the anaplastic lymphoma kinase (ALK) is frequently translocated and a fusion protein with nucleophosmin (NPM)-ALK is generated that contains kinase activity. NPM-ALK transforms fibroblasts, however in BCAR1-/- fibroblasts NPM-ALK fails to induce transformation. Hence, BCAR1 is critical for ALK transformation activity (Ambrogio et al., 2005).
  
  
Entity Chemotherapeutic resistance
Note Overexpression of BCAR1 is linked to drug resistance in multiple tumor types such as breast cancer, lung cancers, glioblastoma and melanoma (Ta et al., 2008). BCAR1 and NEDD9 interact with BCAR3 to mediate anti-estrogen resistance and to control Rap1 GTPase activation (Cai et al., 2003). In a screen of an estrogen dependent cell line, BCAR1 was identified as a gene required for tamoxifen resistance (Brinkman et al., 2000; van der Flier et al., 2000).
  
  
Entity Role of BCAR1 in other pathological conditions or diseases
Note BCAR1 dysfunction is linked to inflammatory disorders, ischemic stroke (Ziemka-Nalecz et al., 2007; Zalewska et al., 2005) and developmental defects. Knockout of BCAR1 is lethal at embryonic stages days 11,5 to 12,5 as a result of cardiovascular dysfunction (Honda et al., 1998). BCAR1 is critical for the pathology of many infectious diseases. The bacterial species Yersinia encodes and secretes a phosphatase YOP that inactivates/dephosphorylates BCAR1 and YOP activity minimizes phagocytosis by macrophages and neutrophils facilitating Yersinia evasion of components of the cellular immune response which disrupts clearance of the bacteria by the host (Deleuil et al., 2003; Hamid et al., 1999). In contrast, in epithelial cells, Yersinia uptake is associated with phosphorylation of BCAR1, thus the bacterium triggers BCAR1 phosphorylation to promote the uptake of the organism in non-phagocytic cells (Weidow et al., 2000). S. typhimurium is an obligate intracellular bacterial pathogen that requires eukaryotic cellular uptake for infection. These bacteria utilize host eukaryotic BCAR1 for efficient bacterial uptake and their infectious cycle (Shi et al., 2006). In addition to bacteria, many viruses also utilize the host protein machinery and BCAR1 for their viral propagation. For instance, internalization of adenovirus is initiated by virus binding to host integrin receptors and virus internalization requires BCAR1 phosphorylation (Li et al., 1998; Li et al., 2000).
  

Bibliography

p130Cas mediates the transforming properties of the anaplastic lymphoma kinase.
Ambrogio C, Voena C, Manazza AD, Piva R, Riera L, Barberis L, Costa C, Tarone G, Defilippi P, Hirsch E, Boeri Erba E, Mohammed S, Jensen ON, Palestro G, Inghirami G, Chiarle R.
Blood. 2005 Dec 1;106(12):3907-16. Epub 2005 Aug 16.
PMID 16105984
 
The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to p130cas.
Astier A, Avraham H, Manie SN, Groopman J, Canty T, Avraham S, Freedman AS.
J Biol Chem. 1997 Jan 3;272(1):228-32.
PMID 8995252
 
Tac-beta1 inhibits FAK activation and Src signaling.
Berrier AL, Jones CW, LaFlamme SE.
Biochem Biophys Res Commun. 2008 Mar 28;368(1):62-7. Epub 2008 Jan 14.
PMID 18198129
 
Crk-associated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRC-transformed cells.
Brabek J, Constancio SS, Siesser PF, Shin NY, Pozzi A, Hanks SK.
Mol Cancer Res. 2005 Jun;3(6):307-15.
PMID 15972849
 
The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle.
Briknarova K, Nasertorabi F, Havert ML, Eggleston E, Hoyt DW, Li C, Olson AJ, Vuori K, Ely KR.
J Biol Chem. 2005 Jun 10;280(23):21908-14. Epub 2005 Mar 28.
PMID 15795225
 
BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells.
Brinkman A, van der Flier S, Kok EM, Dorssers LC.
J Natl Cancer Inst. 2000 Jan 19;92(2):112-20.
PMID 10639512
 
The identification of p130cas-binding proteins and their role in cellular transformation.
Burnham MR, Harte MT, Richardson A, Parsons JT, Bouton AH.
Oncogene. 1996 Jun 6;12(11):2467-72.
PMID 8649789
 
p130Cas is an essential transducer element in ErbB2 transformation.
Cabodi S, Tinnirello A, Bisaro B, Tornillo G, del Pilar Camacho-Leal M, Forni G, Cojoca R, Iezzi M, Amici A, Montani M, Eva A, Di Stefano P, Muthuswamy SK, Tarone G, Turco E, Defilippi P.
FASEB J. 2010 Oct;24(10):3796-808. Epub 2010 May 26.
PMID 20505116
 
Integrin signalling adaptors: not only figurants in the cancer story.
Cabodi S, del Pilar Camacho-Leal M, Di Stefano P, Defilippi P.
Nat Rev Cancer. 2010 Dec;10(12):858-70. Epub 2010 Nov 24. (REVIEW)
PMID 21102636
 
AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter.
Cai D, Iyer A, Felekkis KN, Near RI, Luo Z, Chernoff J, Albanese C, Pestell RG, Lerner A.
Cancer Res. 2003 Oct 15;63(20):6802-8.
PMID 14583477
 
Celecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas.
Casanova I, Parreno M, Farre L, Guerrero S, Cespedes MV, Pavon MA, Sancho FJ, Marcuello E, Trias M, Mangues R.
Int J Cancer. 2006 May 15;118(10):2381-9.
PMID 16353145
 
Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism.
Deleuil F, Mogemark L, Francis MS, Wolf-Watz H, Fallman M.
Cell Microbiol. 2003 Jan;5(1):53-64.
PMID 12542470
 
Breast cancer anti-estrogen resistance protein 1 (BCAR1/p130cas) in pulmonary disease tissue and serum.
Deng B, Huang W, Tan QY, Fan XQ, Jiang YG, Liu L, Zhong YY, Liang YG, Wang RW.
Mol Diagn Ther. 2011 Feb 1;15(1):31-40. doi: 10.2165/11588850-000000000-00000.
PMID 21469768
 
The adaptor proteins p140CAP and p130CAS as molecular hubs in cell migration and invasion of cancer cells.
Di Stefano P, Leal MP, Tornillo G, Bisaro B, Repetto D, Pincini A, Santopietro E, Sharma N, Turco E, Cabodi S, Defilippi P.
Am J Cancer Res. 2011;1(5):663-73. Epub 2011 May 2.
PMID 21994904
 
Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells.
Donaldson JC, Dempsey PJ, Reddy S, Bouton AH, Coffey RJ, Hanks SK.
Exp Cell Res. 2000 Apr 10;256(1):168-78.
PMID 10739664
 
The prognostic value of BCAR1 in patients with primary breast cancer.
Dorssers LC, Grebenchtchikov N, Brinkman A, Look MP, van Broekhoven SP, de Jong D, Peters HA, Portengen H, Meijer-van Gelder ME, Klijn JG, van Tienoven DT, Geurts-Moespot A, Span PN, Foekens JA, Sweep FC.
Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6194-202.
PMID 15448007
 
Carcinoma matrix controls resistance to cisplatin through talin regulation of NF-kB.
Eberle KE, Sansing HA, Szaniszlo P, Resto VA, Berrier AL.
PLoS One. 2011;6(6):e21496. Epub 2011 Jun 24.
PMID 21720550
 
The integrin signalling adaptor p130CAS is also a key player in prostate cancer.
Fromont G, Cussenot O.
Nat Rev Cancer. 2011 Mar;11(3):227.
PMID 21346785
 
BCAR1 expression in prostate cancer: association with 16q23 LOH status, tumor progression and EGFR/KAI1 staining.
Fromont G, Vallancien G, Validire P, Levillain P, Cussenot O.
Prostate. 2007 Feb 15;67(3):268-73.
PMID 17192874
 
p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor.
Gotoh T, Cai D, Tian X, Feig LA, Lerner A.
J Biol Chem. 2000 Sep 29;275(39):30118-23.
PMID 10896938
 
Relation among p130Cas, E-cadherin and beta-catenin expression, clinicopathologic significance and prognosis in human hepatocellular carcinoma.
Guo C, Liu QG, Yang W, Zhang ZL, Yao YM.
Hepatobiliary Pancreat Dis Int. 2008 Oct;7(5):490-6.
PMID 18842495
 
YopH dephosphorylates Cas and Fyn-binding protein in macrophages.
Hamid N, Gustavsson A, Andersson K, McGee K, Persson C, Rudd CE, Fallman M.
Microb Pathog. 1999 Oct;27(4):231-42.
PMID 10502464
 
p130Cas.
Hanks SK, Brabek J.
UCSD Nature Molecule Pages. 2005 Oct 10; Protein A001708.
 
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
 
Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas.
Honda H, Oda H, Nakamoto T, Honda Z, Sakai R, Suzuki T, Saito T, Nakamura K, Nakao K, Ishikawa T, Katsuki M, Yazaki Y, Hirai H.
Nat Genet. 1998 Aug;19(4):361-5.
PMID 9697697
 
Networks of interaction of p120cbl and p130cas with Crk and Grb2 adaptor proteins.
Khwaja A, Hallberg B, Warne PH, Downward J.
Oncogene. 1996 Jun 20;12(12):2491-8.
PMID 8700507
 
The 31-kDa caspase-generated cleavage product of p130cas functions as a transcriptional repressor of E2A in apoptotic cells.
Kim W, Kook S, Kim DJ, Teodorof C, Song WK.
J Biol Chem. 2004 Feb 27;279(9):8333-42. Epub 2003 Dec 2.
PMID 14660614
 
CAS/Crk coupling serves as a "molecular switch" for induction of cell migration.
Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA.
J Cell Biol. 1998 Feb 23;140(4):961-72.
PMID 9472046
 
Association of p130CAS with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry.
Li E, Stupack DG, Brown SL, Klemke R, Schlaepfer DD, Nemerow GR.
J Biol Chem. 2000 May 12;275(19):14729-35.
PMID 10799562
 
CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases.
Nakamoto T, Yamagata T, Sakai R, Ogawa S, Honda H, Ueno H, Hirano N, Yazaki Y, Hirai H.
Mol Cell Biol. 2000 Mar;20(5):1649-58.
PMID 10669742
 
Organization of functional domains in the docking protein p130Cas.
Nasertorabi F, Garcia-Guzman M, Briknarova K, Larsen E, Havert ML, Vuori K, Ely KR.
Biochem Biophys Res Commun. 2004 Nov 19;324(3):993-8.
PMID 15485652
 
Silencing of p130cas in ovarian carcinoma: a novel mechanism for tumor cell death.
Nick AM, Stone RL, Armaiz-Pena G, Ozpolat B, Tekedereli I, Graybill WS, Landen CN, Villares G, Vivas-Mejia P, Bottsford-Miller J, Kim HS, Lee JS, Kim SM, Baggerly KA, Ram PT, Deavers MT, Coleman RL, Lopez-Berestein G, Sood AK.
J Natl Cancer Inst. 2011 Nov 2;103(21):1596-612. Epub 2011 Sep 28.
PMID 21957230
 
Interdependence of cell attachment and cell cycle signaling.
Pugacheva EN, Roegiers F, Golemis EA.
Curr Opin Cell Biol. 2006 Oct;18(5):507-15. Epub 2006 Aug 17. (REVIEW)
PMID 16919436
 
A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner.
Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Mano H, Yazaki Y, Hirai H.
EMBO J. 1994 Aug 15;13(16):3748-56.
PMID 8070403
 
Integrin alphabeta1, alphavbeta, alpha6beta effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance.
Sansing HA, Sarkeshik A, Yates JR, Patel V, Gutkind JS, Yamada KM, Berrier AL.
Biochem Biophys Res Commun. 2011 Mar 11;406(2):171-6. Epub 2011 Feb 1.
PMID 21291860
 
Force sensing by mechanical extension of the Src family kinase substrate p130Cas.
Sawada Y, Tamada M, Dubin-Thaler BJ, Cherniavskaya O, Sakai R, Tanaka S, Sheetz MP.
Cell. 2006 Dec 1;127(5):1015-26.
PMID 17129785
 
Invasion of host cells by Salmonella typhimurium requires focal adhesion kinase and p130Cas.
Shi J, Casanova JE.
Mol Biol Cell. 2006 Nov;17(11):4698-708. Epub 2006 Aug 16.
PMID 16914515
 
Urinary-type plasminogen activator receptor (uPAR) modulates oral cancer cell behavior with alteration in p130cas.
Shi Z, Liu Y, Johnson JJ, Stack MS.
Mol Cell Biochem. 2011 Nov;357(1-2):151-61. Epub 2011 Jun 1.
PMID 21630091
 
A novel association between p130Cas and resistance to the chemotherapeutic drug adriamycin in human breast cancer cells.
Ta HQ, Thomas KS, Schrecengost RS, Bouton AH.
Cancer Res. 2008 Nov 1;68(21):8796-804.
PMID 18974122
 
NEDD9 and BCAR1 negatively regulate E-cadherin membrane localization, and promote E-cadherin degradation.
Tikhmyanova N, Golemis EA.
PLoS One. 2011;6(7):e22102. Epub 2011 Jul 12.
PMID 21765937
 
Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by alpha1-integrins during colon cancer cell invasion.
Van Slambrouck S, Grijelmo C, De Wever O, Bruyneel E, Emami S, Gespach C, Steelant WF.
Int J Oncol. 2007 Dec;31(6):1501-8.
PMID 17982677
 
Focal adhesion formation by F9 embryonal carcinoma cells after vinculin gene disruption.
Volberg T, Geiger B, Kam Z, Pankov R, Simcha I, Sabanay H, Coll JL, Adamson E, Ben-Ze'ev A.
J Cell Sci. 1995 Jun;108 ( Pt 6):2253-60.
PMID 7673345
 
Introduction of p130cas signaling complex formation upon integrin-mediated cell adhesion: a role for Src family kinases.
Vuori K, Hirai H, Aizawa S, Ruoslahti E.
Mol Cell Biol. 1996 Jun;16(6):2606-13.
PMID 8649368
 
Tyrosine phosphorylation of p130Cas and cortactin accompanies integrin-mediated cell adhesion to extracellular matrix.
Vuori K, Ruoslahti E.
J Biol Chem. 1995 Sep 22;270(38):22259-62.
PMID 7545676
 
CAS/Crk signalling mediates uptake of Yersinia into human epithelial cells.
Weidow CL, Black DS, Bliska JB, Bouton AH.
Cell Microbiol. 2000 Dec;2(6):549-60.
PMID 11207607
 
Colon cancer chemopreventive drugs modulate integrin-mediated signaling pathways.
Weyant MJ, Carothers AM, Bertagnolli ME, Bertagnolli MM.
Clin Cancer Res. 2000 Mar;6(3):949-56.
PMID 10741720
 
Multiparametric analysis of focal adhesion formation by RNAi-mediated gene knockdown.
Winograd-Katz SE, Itzkovitz S, Kam Z, Geiger B.
J Cell Biol. 2009 Aug 10;186(3):423-36.
PMID 19667130
 
Members of the Zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers.
Yi J, Kloeker S, Jensen CC, Bockholt S, Honda H, Hirai H, Beckerle MC.
J Biol Chem. 2002 Mar 15;277(11):9580-9. Epub 2002 Jan 8.
PMID 11782456
 
Neonatal cerebral hypoxia-ischemia: involvement of FAK-dependent pathway.
Zalewska T, Makarewicz D, Janik B, Ziemka-Nalecz M.
Int J Dev Neurosci. 2005 Nov;23(7):657-62. Epub 2005 Aug 10.
PMID 16095866
 
Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal polyps: an immunohistochemical study.
Zhang PJ, Weber R, Liang HH, Pasha TL, LiVolsi VA.
Arch Pathol Lab Med. 2003 Nov;127(11):1480-4.
PMID 14567719
 
The docking protein p130Cas regulates cell sensitivity to proteasome inhibition.
Zhao M, Vuori K.
BMC Biol. 2011 Oct 28;9:73.
PMID 22034875
 
Transient forebrain ischemia effects FAK-coupled signaling in gerbil hippocampus.
Ziemka-Nalecz M, Zalewska T.
Neurochem Int. 2007 Nov-Dec;51(6-7):405-11. Epub 2007 Apr 22.
PMID 17524523
 
Bcar1/p130Cas protein and primary breast cancer: prognosis and response to tamoxifen treatment.
van der Flier S, Brinkman A, Look MP, Kok EM, Meijer-van Gelder ME, Klijn JG, Dorssers LC, Foekens JA.
J Natl Cancer Inst. 2000 Jan 19;92(2):120-7.
PMID 10639513
 

Citation

This paper should be referenced as such :
Berrier, A
BCAR1 (breast cancer anti-estrogen resistance 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(5):329-335.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BCAR1ID761ch16q23.html

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;11)(p25;p15) ANKRD28/NUP98

External links

Nomenclature
HGNC (Hugo)BCAR1   971
Cards
AtlasBCAR1ID761ch16q23
Entrez_Gene (NCBI)BCAR1  9564  BCAR1, Cas family scaffolding protein
AliasesCAS; CAS1; CASS1; CRKAS; 
P130Cas
GeneCards (Weizmann)BCAR1
Ensembl hg19 (Hinxton)ENSG00000050820 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000050820 [Gene_View]  chr16:75228187-75251656 [Contig_View]  BCAR1 [Vega]
ICGC DataPortalENSG00000050820
TCGA cBioPortalBCAR1
AceView (NCBI)BCAR1
Genatlas (Paris)BCAR1
WikiGenes9564
SOURCE (Princeton)BCAR1
Genetics Home Reference (NIH)BCAR1
Genomic and cartography
GoldenPath hg38 (UCSC)BCAR1  -     chr16:75228187-75251656 -  16q23.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)BCAR1  -     16q23.1   [Description]    (hg19-Feb_2009)
EnsemblBCAR1 - 16q23.1 [CytoView hg19]  BCAR1 - 16q23.1 [CytoView hg38]
Mapping of homologs : NCBIBCAR1 [Mapview hg19]  BCAR1 [Mapview hg38]
OMIM602941   
Gene and transcription
Genbank (Entrez)AB040024 AF218451 AJ242987 AK026121 AK027608
RefSeq transcript (Entrez)NM_001170714 NM_001170715 NM_001170716 NM_001170717 NM_001170718 NM_001170719 NM_001170720 NM_001170721 NM_014567
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)BCAR1
Cluster EST : UnigeneHs.479747 [ NCBI ]
CGAP (NCI)Hs.479747
Alternative Splicing GalleryENSG00000050820
Gene ExpressionBCAR1 [ NCBI-GEO ]   BCAR1 [ EBI - ARRAY_EXPRESS ]   BCAR1 [ SEEK ]   BCAR1 [ MEM ]
Gene Expression Viewer (FireBrowse)BCAR1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9564
GTEX Portal (Tissue expression)BCAR1
Human Protein AtlasENSG00000050820-BCAR1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP56945   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP56945  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP56945
Splice isoforms : SwissVarP56945
PhosPhoSitePlusP56945
Domaine pattern : Prosite (Expaxy)SH3 (PS50002)   
Domains : Interpro (EBI)BCAR1    CAS_DUF3513    Serine_rich    SH3_domain    Spectrin_alpha_SH3   
Domain families : Pfam (Sanger)DUF3513 (PF12026)    Serine_rich (PF08824)    SH3_1 (PF00018)   
Domain families : Pfam (NCBI)pfam12026    pfam08824    pfam00018   
Domain families : Smart (EMBL)SH3 (SM00326)  
Conserved Domain (NCBI)BCAR1
DMDM Disease mutations9564
Blocks (Seattle)BCAR1
PDB (SRS)1WYX    3T6G   
PDB (PDBSum)1WYX    3T6G   
PDB (IMB)1WYX    3T6G   
PDB (RSDB)1WYX    3T6G   
Structural Biology KnowledgeBase1WYX    3T6G   
SCOP (Structural Classification of Proteins)1WYX    3T6G   
CATH (Classification of proteins structures)1WYX    3T6G   
SuperfamilyP56945
Human Protein Atlas [tissue]ENSG00000050820-BCAR1 [tissue]
Peptide AtlasP56945
HPRD04248
IPIIPI00872386   IPI00646673   IPI00954861   IPI00954889   IPI00011998   IPI00641339   IPI00954913   IPI00954799   IPI01018330   IPI00645994   
Protein Interaction databases
DIP (DOE-UCLA)P56945
IntAct (EBI)P56945
FunCoupENSG00000050820
BioGRIDBCAR1
STRING (EMBL)BCAR1
ZODIACBCAR1
Ontologies - Pathways
QuickGOP56945
Ontology : AmiGOregulation of cell growth  ruffle  signal transducer activity  protein binding  cytoplasm  cytosol  plasma membrane  focal adhesion  focal adhesion  actin filament organization  cell adhesion  epidermal growth factor receptor signaling pathway  G-protein coupled receptor signaling pathway  G-protein coupled receptor signaling pathway  integrin-mediated signaling pathway  cell proliferation  insulin receptor signaling pathway  positive regulation of endothelial cell migration  actin cytoskeleton  cell migration  SH3 domain binding  protein kinase binding  lamellipodium  positive regulation of cell migration  cellular response to hepatocyte growth factor stimulus  regulation of apoptotic process  platelet-derived growth factor receptor signaling pathway  vascular endothelial growth factor receptor signaling pathway  vascular endothelial growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  hepatocyte growth factor receptor signaling pathway  antigen receptor-mediated signaling pathway  T cell receptor signaling pathway  B cell receptor signaling pathway  cell division  cell chemotaxis  
Ontology : EGO-EBIregulation of cell growth  ruffle  signal transducer activity  protein binding  cytoplasm  cytosol  plasma membrane  focal adhesion  focal adhesion  actin filament organization  cell adhesion  epidermal growth factor receptor signaling pathway  G-protein coupled receptor signaling pathway  G-protein coupled receptor signaling pathway  integrin-mediated signaling pathway  cell proliferation  insulin receptor signaling pathway  positive regulation of endothelial cell migration  actin cytoskeleton  cell migration  SH3 domain binding  protein kinase binding  lamellipodium  positive regulation of cell migration  cellular response to hepatocyte growth factor stimulus  regulation of apoptotic process  platelet-derived growth factor receptor signaling pathway  vascular endothelial growth factor receptor signaling pathway  vascular endothelial growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  hepatocyte growth factor receptor signaling pathway  antigen receptor-mediated signaling pathway  T cell receptor signaling pathway  B cell receptor signaling pathway  cell division  cell chemotaxis  
Pathways : BIOCARTAIntegrin Signaling Pathway [Genes]    CXCR4 Signaling Pathway [Genes]    Cell to Cell Adhesion Signaling [Genes]    Links between Pyk2 and Map Kinases [Genes]    PTEN dependent cell cycle arrest and apoptosis [Genes]   
Pathways : KEGGFocal adhesion    Leukocyte transendothelial migration    Regulation of actin cytoskeleton   
REACTOMEP56945 [protein]
REACTOME PathwaysR-HSA-8849471 [pathway]   
NDEx NetworkBCAR1
Atlas of Cancer Signalling NetworkBCAR1
Wikipedia pathwaysBCAR1
Orthology - Evolution
OrthoDB9564
GeneTree (enSembl)ENSG00000050820
Phylogenetic Trees/Animal Genes : TreeFamBCAR1
HOVERGENP56945
HOGENOMP56945
Homologs : HomoloGeneBCAR1
Homology/Alignments : Family Browser (UCSC)BCAR1
Gene fusions - Rearrangements
Fusion : QuiverBCAR1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBCAR1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BCAR1
dbVarBCAR1
ClinVarBCAR1
1000_GenomesBCAR1 
Exome Variant ServerBCAR1
ExAC (Exome Aggregation Consortium)ENSG00000050820
GNOMAD BrowserENSG00000050820
Genetic variants : HAPMAP9564
Genomic Variants (DGV)BCAR1 [DGVbeta]
DECIPHERBCAR1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisBCAR1 
Mutations
ICGC Data PortalBCAR1 
TCGA Data PortalBCAR1 
Broad Tumor PortalBCAR1
OASIS PortalBCAR1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBCAR1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDBCAR1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch BCAR1
DgiDB (Drug Gene Interaction Database)BCAR1
DoCM (Curated mutations)BCAR1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BCAR1 (select a term)
intoGenBCAR1
NCG5 (London)BCAR1
Cancer3DBCAR1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602941   
Orphanet
DisGeNETBCAR1
MedgenBCAR1
Genetic Testing Registry BCAR1
NextProtP56945 [Medical]
TSGene9564
GENETestsBCAR1
Target ValidationBCAR1
Huge Navigator BCAR1 [HugePedia]
snp3D : Map Gene to Disease9564
BioCentury BCIQBCAR1
ClinGenBCAR1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9564
Chemical/Pharm GKB GenePA25281
Clinical trialBCAR1
Miscellaneous
canSAR (ICR)BCAR1 (select the gene name)
Probes
Litterature
PubMed225 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBCAR1
EVEXBCAR1
GoPubMedBCAR1
iHOPBCAR1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

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indexed on : Mon May 14 12:32:23 CEST 2018
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