| Written | 2009-02 | Sheri FT Fong, Keith SK Fong, Katalin Csiszar |
| John A. Burns School of Medicine, University of Hawaii, 1960 East West Road, Biomed T415, Honolulu, HI 96822, USA |
| Identity |
| Other alias | |
| HGNC (Hugo) | LOX |
| LocusID (NCBI) | 4015 |
| Atlas_Id | 41191 |
| Location | 5q23.1 [Link to chromosome band 5q23] |
| Location_base_pair | Starts at 122063195 and ends at 122078501 bp from pter ( according to hg19-Feb_2009) [Mapping LOX.png] |
| Local_order | FTMT - SRFBP1 - LOX - ZNF474 - SNCAIP |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| CORO7-PAM16 (16p13.3) / LOX (5q23.1) | LOX (5q23.1) / LOC642852 (21q22.3) |
| DNA/RNA |
 | |
| Figure 1. Lysyl oxidase gene structure. Exons are depicted as boxes separated by intron sequences (solid lines). The size of each exon and intron is shown in base pairs, above (exons) and below (introns) of the gene, respectively. The exons shaded in red encode amino acids sequences that are conserved in all lysyl oxidase family members. The exon shaded in blue contains the 3' UTR sequence. | |
| Description | The LOX gene is composed of seven exons and six introns, distributed through approximately 14.5 kb of genomic DNA (Hamalainen et al., 1993; Boyd et al., 1995). Three transcripts of sizes 2.0 kb, 3.8 kb and 4.8 kb are produced (Mariani et al., 1992), as a consequence of differential use of several polyadenylation signals within the 3' UTR (Boyd et al., 1995). There is a heritable restriction fragment length polymorphism within a PstI restriction site in the first exon (Csiszar et al., 1993). Three additional polymorphisms were also identified: Ala75Ala, Arg103Pro, Arg158Gln (Kaneda et al., 2004). There are no microsatellites within the LOX gene, but three have been described in the LOX gene locus within 20 kb and 5 kb centromeric, and 7 kb telomeric to the LOX gene (Csiszar et al., 2002). The 5' region of LOX also contains a CpG island which extends into exon 1 (Kaneda et al., 2002; Kaneda et al., 2004). |
| Transcription | The rat LOX promoter contains a metal-response element, a hypoxia-response element, an antioxidant-response element, at least four positive regulatory segments and 2 negative regulatory segments. Multiple transcriptional start sites have been described (Gao et al., 2007). The regulation of LOX gene expression has been described in different tissues and cells from several species, and has revealed multiple complex mechanisms that regulate the expression and activity of LOX. Many of these effectors are reviewed in Csiszar, 2001, and encompass cytokines and growth factors, such as fibroblast growth factor, basic fibroblast growth factor, insulin-like growth factor-1, interferon-gamma and transforming growth factor-beta; hormones and mediators, such as testosterone, progestin and prostaglandin E2; signaling molecules, such as cAMP, interferon regulatory factor-1 and ras; and drugs, such as adriamycin, bleomycin and hydralazine. Additional effectors have since been described, including follicle stimulating hormone (Slee et al., 2001; Harlow et al., 2003), hyperosmotic solution (Omori et al., 2002), secretory leukocyte protease inhibitor (Zhang et al., 2002), interleukin-1alpha (Rae et al., 2004), cigarette smoke condensate (Chen et al., 2005; Gao et al., 2005), tumor necrosis factor-alpha (Rodriguez et al., 2008), granulocyte macrophage colony-stimulating factor (Weissen-Plenz et al., 2008), hyaluronan with insulin-like growth factor-1 (Kothapalli and Ramamurthi, 2008) and parathyroid hormone (Lowry et al., 2008). LOX expression is promoted in MCF-7 breast cancer cells by contact with fibroblast-conditioned media, collagen I matrix conditioned by fibroblasts (Kirschmann et al., 2002), and in HK-2 renal proximal tubule cells co-cultured with HMEC-1 microvascular endothelial cells (Aydin et al., 2008). LOX expression is also induced by hypoxia. Hypoxia-inducible factor-1alpha (HIF-1alpha) stimulates LOX mRNA transcription (Erler et al., 2006; Higgins et al., 2007). LOX expression in hypoxia can be modulated by pH (Sorensen et al., 2007). The recruitment of HIF-1alpha to the LOX promoter is potentiated by Notch, which also increases Snail-1 expression (Sahlgren et al., 2008). Transcription of the LOX gene is also affected by the methylation status of its CpG island (Kaneda et al., 2002; Kaneda et al., 2004). |
| Pseudogene | No known pseudogene. |
| Protein |
 | |
| Figure 2. Lysyl oxidase protein structure. All members of the lysyl oxidase family of proteins share two highly conserved domains: a unique copper-binding (Cu) domain containing four histidines, shaded in red; and a cytokine-receptor like (CRL) domain similar to type I cytokine receptors, shaded in green. The predicted signal sequence is shaded in purple. The BMP-1 cleavage site, shaded in yellow, is noted by the arrow. | |
| Description | The lysyl oxidase transcript encodes for a 417-amino acid protein, including a signal peptide of 21 amino acids (Hamalainen et al., 1991; Mariani et al., 1992). Removal of the signal sequence and N-glycosylation within the propeptide region produces a 50 kDa proenzyme (Trackman et al., 1992). Incorporation of copper is thought to occur either in the endoplasmic reticulum or in the Golgi in prior to and independently of glycosylation (Kosonen et al., 1997). After secretion into the extracellular space, the mature, non-glycosylated 32 kDa protein (Trackman et al., 1992) is generated by proteolytic cleavage of the propeptide region between Gly-168 and Asp-169 by C-proteinase (Cronshaw et al., 1995), encoded by the bone morphogenic protein-1 (BMP-1), and the related tolloid-like-1 and -2 (Kessler et al., 1996; Uzel et al., 2001). LOX may also be a substrate of human meprin, an astacin-like metallopeptidase belonging to the same subfamily as BMP-1 and mammalian tolloid (Ambort et al., 2008). |
| Expression | As LOX is necessary for the assembly and tensile strength and mechanical stability of collagen fibrils, and for the assembly and repetitive and reversible deformation of elastin, it is highly expressed in tissues containing fibrillar collagen and/or elastic fibers. These include skin, lung, cartilage, the cardiovascular system and the fibrous laminia propria in the small intestine. LOX was also detected in the liver, kidney, stomach, retina, and brain (Hayashi et al., 2004). In the eye, LOX has been identified in the vitreous, iris/ciliary body, lens, choroid/retinal pigment epithelium and retina (Coral et al., 2008). LOX has also been described in the mesencephalon, corpus callosum, cerebral cortex and cerebellum of the brain (Laczko et al., 2007). Protein expression of LOX may be influenced by microRNAs. The 3' UTR of LOX mRNA contains a binding site for mir-145, which is down-regulated in many cancers (Dalmay and Edwards, 2006). |
| Localisation | LOX has been classically characterized as an extracellular matrix enzyme (Kagan and Trackman, 1991). However, less is known about intracellular LOX. The LOX protein has been localized within the nuclei of various cells and tissues (Li et al., 1997; Hayashi et al., 2004; Li et al., 2004), and retains its catalytic activity inhibited by beta-aminopropionitrile (bAPN) (Li et al., 1997). Nuclear LOX has been shown to originate from extracellular LOX that enters the cytosol and concentrates within the nucleus (Nellaiappan et al., 2000). Histones have been reported as substrates for lysyl oxidase (Kagan et al, 1983; Giampuzzi et al, 2003), and transfection of LOX yielded less tightly packed chromatin (Mello et al., 1995). Electron microscopy confirmed association of LOX with condensed chromatin in the nucleus (Kagan and Li, 2003). In addition to its nuclear localization, LOX has also been identified in the cytoplasm of numerous cells and tissues (Wakasaki and Ooshima, 1990; Kobayashi et al., 1994; Hayashi et al., 2004; Jansen and Csiszar, 2007). This cytoplasmic LOX was localized to cytoskeletal filaments and microtubule networks (Wakasaki and Ooshima, 1990; Guo et al., 2007). The propeptide of LOX (LOX-PP), which has been described to have a different function than the LOX enzyme, differs in its localization compared to the active LOX enzyme, and is dependent on cell stage. LOX-PP, which is generated extracellularly, is able to reenter the cells. In differentiating osteoblasts, both LOX-PP and LOX enzyme localized to the cytoplasm associated with tubulin and the microtubule network, while in proliferating osteoblasts, LOX-PP localized perinuclearly in the Golgi complex and endoplasmic reticulum while LOX enzyme was mainly in the nucleus (Guo et al., 2007). |
| Function | Lysyl oxidase oxidizes peptidyl lysine and hydroxylysine residues in collagen and lysine residues in elastin to produce peptidyl alpha-aminoadipic-delta-semialdehydes. These aldehyde residues can spontaneously condense with vicinal peptidyl aldehydes or with epsilon-amino groups of peptidyl lysine to form the covalent cross-links that stabilize and insolubilize several fibrillar collagen types and elastin fibers (reviewed in Lucero and Kagan, 2006). This catalytic reaction can be irreversibly inhibited by bAPN, a specific inhibitor that binds to the active site of LOX (Tang et al., 1983). Semicarbazide is a partial inhibitor of LOX (Mercier et al., 2007), as is 2-mercaptopyridine-N-oxide, although it acts through a different mechanism than bAPN (Anderson et al., 2007). Pathological concentrations of homocysteine also inhibit LOX activity (Raposa et al., 2004). The activity of LOX in the extracellular matrix may be coordinated by its interaction with fibronectin (Fogelgren et al, 2005). The critical nature of LOX enzyme activity was demonstrated in the LOX "knockout" mouse, which expires immediately after birth due to rupture of the aorta and diaphragm from incomplete cross-linking of elastin (Maki et al., 2002; Hornstra et al., 2003). Local administration of LOX resulted in inhibition of abdominal aortic aneurysm development in a mouse model (Yoshimura et al., 2006). LOX is also essential for development of the distal and proximal airways, and alveolarization in the lungs (Maki et al., 2005), and is increased in preterm lamb lungs compared to full-term (Bland et al., 2007). In zebrafish, LOX is critical for notochord formation and muscle development (Anderson et al., 2007; Gansner et al., 2007; Reynaud et al., 2008), a process that may involve the fibrillin-2 gene or alpha1 chain of type VIII collagen (Gansner et al., 2008; Gansner and Gitlin, 2008). In sea urchins, inhibition of LOX caused developmental arrest at the mesenchymal blastula state (Butler et al., 1987), and in Xenopus laevis, LOX was shown to antagonize p21-Ha-Ras-induced and progesterone-dependent oocyte maturation (Di Donato et al., 1997). LOX also has a role in cell differentiation. LOX was identified as an early marker in adipocyte differentiation responsive to retinoic acid (Dimaculangan et al., 1994). Increased LOX may affect osteoblastic differentiation through cross-link formation in the surrounding collagen matrix (Kaku et al., 2007; Turecek et al., 2008). LOX may also modulate cartilage growth (Asanbaeva et al., 2008). Alterations in LOX expression were observed in development and aging of the skin, as well as physiological and pathological processes of the skin, including wound healing, fibrosis, hypertrophic scarring, keloids, and scleroderma (reviewed in Szauter et al., 2005). Inhibition of LOX activity resulted in inhibition of skin graft contraction in a human skin model (Harrison et al., 2006) Decreased LOX expression was noted in pelvic organ prolapse (Klutke et al., 2008), in pregnant mouse vagina and cervix compared to non-pregnant and post-partum tissues (Drewes et al., 2007), in proliferative diabetic retinopathy and rhegmatogenous retinal detachment (Coral et al., 2008), and early atherosclerosis (reviewed in Rodriguez et al., 2008). Induction of LOX was reported in inflamed oral tissue (Trackman et al., 1998) and gingival atrophy from experimental occlusal hypofunction (Ishida et al., 2008); rheumatoid arthritis (Kaufmann et al., 2003); inflammatory bowel disease (Rivera et al., 2006); liver stiffness preceding liver fibrosis (Georges et al., 2007); fibrosis of the liver (reviewed in Kagan, 1994), lung (Counts et al., 1981; Almassian et al., 1991; Peyrol et al., 1997), kidney (Di Donato et al., 1997; Goto et al., 2005; Higgins et al., 2007), oral submucosa (reviewed in Tilakaratne et al., 2006) and heart (Lopez et al., 2008; Sivakumar et al., 2008; Spurney et al., 2008; Urashima et al., 2008); systemic sclerosis (Meyringer et al., 2007); amyotrophic lateral sclerosis (Malaspina et al., 2001; Li et al., 2004); senile plaque development in Alzheimer's and non-Alzheimer's dementia (Gilad et al., 2005) and stromal reactions in cancer, which are described in more detail below. Besides collagen and elastin, other substrates have been identified for LOX. The oxidation of lysine residues in basic fibroblast growth factor (bFGF) caused covalent crosslinking of bFGF monomers to form dimers and higher order oligomers, leading to reduced mouse fibroblast proliferation (Li et al., 2003). LOX also oxidizes the platelet-derived growth factor (PDGF) receptor beta, which increases its binding affinity for PDGF-BB and decreases the turnover of PDGF receptor beta signal transduction pathway (Lucero et al., 2008). LOX also interacts with mature transforming growth factor-beta (TGF-b). LOX and TGF-b colocalize to mineral associated bone matrix, and LOX was able to suppress TGF-b1-induced Smad3 phosphorylation (Atsawasuwan et al., 2008). LOX has been shown to regulate the promoters of collagen III (COL3A1) and elastin (Giampuzzi et al., 2000; Oleggini et al., 2007; Lelievre et al., 2008). LOX also interacts with histones H1 and H2, and may be able to modulate the condensation status of chromatin to affect transcription of other genes as well (Giampuzzi et al., 2003). LOX has chemokinetic and chemotactic effects on human blood monocytes (Lazarus et al., 1995), a predominantly chemotactic effect on rat vascular smooth muscle cells and mouse embryonic fibroblasts (Li et al., 2000; Lucero et al., 2008), and has been demonstrated to regulate breast cancer cell migration and adhesion and astrocytoma migration through a hydrogen-peroxide mediated mechanism (Payne et al., 2005; Laczko et al., 2007). The same mechanism may also play a role in the promotion of normal breast epithelial cell proliferation and migration by the interaction of LOX and hormone placental lactogen (PL), although PL is not a substrate for LOX (Polgar et al., 2007). The catalytic domain of LOX is able to interact with Snail-1 in vitro, a transcription factor crucial to EMT (Peinado et al., 2005). LOX is responsible for increased migratory ability of renal tubular epithelial cells induced by hypoxia (Higgins et al., 2007). Smooth muscle migration may be modulated through the interaction with VE-statin/egfl7 to inhibit LOX enzyme activity (Lelievre et al., 2008). LOX also interacts and oxidizes PDGF receptor beta to modulate chemokine activity (Lucero et al., 2008). LOX also has multiple roles in cancer, including its opposing effect on ras-transformation, tumor suppression, stromal reaction in cancer, and the promotion of cancer cell adhesion, migration, invasion and metastases, and these are described in more detail in the following sections. |
| Homology | In the human lysyl oxidase protein family, there are five members, named LOX, LOXL1, LOXL2, LOXL3 and LOXL4. They all contain a lysine tyrosylquinone (LTQ), the only mammalian cofactor derived from the cross-linking of two amino acid side chains (reviewed in Anthony, 1996), and which is unique to the LOX family. The other highly conserved motif that is unique to the LOX family is the copper-binding domain, which contains four histidines (Krebs and Krawetz, 1993). All LOX family members also contain a cytokine receptor-like (CRL) domain, which has part of the consensus sequence of Class 1 cytokine receptors (Bazan, 1990). LOX has closest homology to LOXL1, and both seem to be found exclusively in vertebrates. |
| Mutations |
| Note | Despite the implication of LOX in many diseases and disorders, including inflammation and inflammatory diseases, fibrosis of distinct organs and fibrotic disorders, and cancer promotion and progression, there are only sparse reports of any mutations or epigenetic alterations in the LOX gene. |
| Epigenetics | The CpG island of LOX was described to be methylated in 27% of a primary gastric cancer panel. Silencing of LOX expression by methylation was also observed in gastric, colon, lung and ovarian cancer cell lines (Kaneda et al., 2002, Kaneda et al., 2004). Our group has also noted increase in LOX expression following treatment with the demethylating agent, 5-aza-2'-deoxycytidine, in breast cancer cell lines (unpublished data). Methylation is thought to be the mechanism of LOX suppression after ras-transformation (Contente et al., 1999). |
| Somatic | Loss of heterozygosity has been documented in colon and gastric cancers. In 42 colon tumors informative for the microsatellites flanking the LOX gene, 38% demonstrated loss of heterozygosity (Csiszar et al., 2002). In gastric cancer, 33% of 27 informative tumors demonstrated loss of heterozygosity (Kaneda et al., 2004). Somatic mutations of the LOX gene have been documented in colon cancer and possibly, an ovarian cancer cell line. One nonsense mutation that affected codon 332, a 3' rearrangement affecting exons 5-7, and six 5' intragenic alterations or deletions, were detected out of the 8 colon tumors that demonstrated both loss of heterozygosity and reduced LOX expression (Csiszar et al., 2002). Of 96 gastric cancer samples and 58 gastric, lung, colon, ovarian and pancreatic cancer cell lines, only one somatic mutation or rare polymorphism was found in an ovarian cancer cell line: Ala147Gly (Kaneda et al., 2004). The polymorphism Arg158Glu is associated with earlier clinical stage, lower tumor grade and decreased lymph node metastases in oral squamous cell carcinomas. The polymorphism also did not induce anchorage independent growth as did the wild type LOX (Shieh et al., 2007). As point mutations and deletions appear to be infrequent, the loss of LOX expression may be due to a combination of the more frequent loss of heterozygosity and epigenetic regulation. Indeed, some gastric cancers demonstrated biallelic methylation or loss of heterozygosity of one allele with methylation of the other allele (Kaneda et al., 2004). |
| Implicated in |
| Note | |
| Entity | Tumor suppression, stromal reactions and cancer progression |
| Note | Due to its multiple functions both extracellularly and intracellularly, lysyl oxidase has been implicated in several processes in the tumorigenic pathway, in many different cancer types and stages. These are addressed separately below. |
| Entity | Inhibition of ras transformation |
| Note | A putative tumor suppressor gene named the ras recision gene (rrg) was discovered to be greatly reduced in NIH 3T3 cells transformed by LTR-c-H-ras, and re-expressed in revertant cells, despite retaining high levels of ras expression (Contente et al., 1990). Analysis of rrg cDNA revealed that it was lysyl oxidase (Kenyon et al., 1991; Mariani et al., 1992), and the expression of LOX in revertant ras-transformed cells was confirmed by other investigators (Krzyzosiak et al., 1992; Hajnal et al., 1993; Friedman et al., 1997), and in other cell lines such as v-Ki-ras-transformed mouse osteoblastic cells (Shibanuma et al., 1993), EJ-ras-transformed rat fibroblasts (Oberhuber et al., 1995) and c-Ha-ras-transformed human osteosarcoma cell line (Csiszar et al., 1996), and transformed enterocytes (Sagiv et al., 2007). Ras-transformed NIH 3T3 cells transfected with rrg were non-tumorigenic in athymic mice (Contente et al., 1990), and anchorage independence of transformed cells was dependent on down-regulation of rrg (Hajnal et al., 1993). Even in a non-transformed normal rat kidney fibroblast cell line (NRK-49F), down-regulation of LOX was able to induce a oncogenic phenotype accompanied by p21ras activation, phosphorylation of c-jun and up-regulation of beta-catenin and cyclin D1 (Giampuzzi et al., 2001; Giampuzzi et al., 2003; Giampuzzi et al., 2005). The initial loss of LOX expression with ras transformation is thought to be due to methylation (Contente et al., 1999). This counter-effect of ras by LOX was confirmed by the ability of LOX to inhibit ras-induced meiotic maturation downstream of the ras-MEK1-Erk2 pathway in normal Xenopus laevis oocytes, an action that was blocked by bAPN, a selective inhibitor of LOX enzyme activity (DiDonato et al., 1997). In ras-transformed NIH 3T3 cells, LOX was able to partially inhibit MEK kinase activity, but was more potent against PI3K and Akt kinases and blocked membrane localization of Akt and PDK1, preventing activation of NF-kB (Jeay et al., 2003). It was determined that the 18 kD propeptide domain of LOX (LOX-PP), released during proteolytic cleavage to mature LOX, not LOX enzyme activity, was responsible for inducing phenotypic reversion. LOX-PP inhibited ras-transformation, anchorage independent growth and migration of fibroblasts, lung and pancreatic cancer cells (Palakumbura et al., 2004; Wu et al., 2007), and invasive phenotype of Her-2/neu breast cancer (Min et al., 2007). LOX-PP is thought to inhibit ras signaling via Akt and ERK pathways, the expression and activity of downstream effectors NF-kB, Bcl-2 and cyclin D1, and EMT (Min et al., 2007; Wu et al., 2007). LOX-PP inhibits primary rat aorta smooth muscle cell proliferation, DNA synthesis, MMP-9 mRNA expression and TNF-a stimulated Erk 1 / Erk 2 activation (Hurtado et al., 2008). LOX-PP has also been described to attenuate fibronectin-stimulated activation of FAK and its downstream activation of p130Cas, leading to inhibition of fibronectin-stimulated cell migration (Zhao et al., 2009). |
| Entity | Basal and squamous cell carcinoma |
| Note | Lysyl oxidase expression was present in the basal and spinous layers of the epidermis, but absent in basal and squamous cell carcinomas. Silencing of LOX expression in the human keratinocyte cell line, HaCaT, by transfection with anti-sense LOX, induced invasive ability as demonstrated by invasion of the dermis in a skin equivalent model (Bouez et al., 2006). In the stromal reactions around basal and squamous cell carcinoma foci, LOX protein expression indicated the fibrillar reaction and discriminated the tumor-stroma interface of late densely organized desmoplasia (Bouez et al., 2006). |
| Entity | Bone cancer |
| Note | Treatment of human osteosarcoma cells with suramin, an anti-cancer agent, caused decreased proliferation and upregulation of LOX and genes involved in osteoblast differentiation (Buchinger et al., 2008). Mututally subtractive RNA fingerprinted demonstrated up-regulation of LOX in the osteosarcoma cell line, MG63, compared to absent expression in normal osteoblasts (Fuchs et al., 2000). In five closely related murine osteosarcoma cell lines derived from the same tumor, LOX mRNA expression was elevated, but varied, and did not strictly correspond with collagen mRNA levels, insoluble collagen accumulation or LOX enzyme activity (Uzel et al., 2000). |
| Entity | Brain cancer |
| Note | LOX was found to be highly expressed in a panel of glioblastoma cell lines (Ross et al., 2000). Gene expression profiling of gliomas identified over-expressed lysyl oxidase as part of a molecular signature indicative of invasion, and associated with higher-grade tumors that are strongly correlated with poor patient survival (Freije et al., 2004). LOX protein expression was increased in glioblastoma and astrocytoma tissues, and in invasive U343 and U251 cultured astrocytoma cells. LOX was shown to be responsible for astrocytoma cell migration and FAK and paxillin phosphorylation (Laczko et al., 2007). |
| Entity | Breast cancer |
| Note | LOX-PP is able to attenuate fibronectin-stimulated activation of FAK and its downstream activation of p130Cas, leading to inhibition of fibronectin-stimulated breast cancer cell migration (Zhao et al., 2008). LOX mRNA expression was down-regulated in invasive breast cancer tumor vasculature compared to normal vasculature, indicating that LOX may be involved in regulating tumor vasculature plasticity (Parker et al., 2004). LOX could be detected at the invasion front of infiltrating breast tumors, but decreased in late stromal reactions and disappeared from the stroma of invading ductal carcinomas (Peyrol et al., 1997). LOX mRNA was demonstrated to be up-regulated in the invasive and metastatic cell lines, MDA-MB-231 and Hs578T, compared to the poorly-invasive and non-metastatic cell lines, MCF-7 and T47D, as well as in more aggressive breast cancer cell lines and distant metastatic tissues compared with primary cancer tissues (reviewed in Payne et al., 2007; Nagaraja et al., 2006; Mbeunkui et al., 2007). Transfection of MDA-MB-231 and Hs578T with antisense LOX, resulted in repression of invasive ability. Treatment of MDA-MB-231 and Hs578T with bAPN also inhibited invasive ability as well as cell migration and adhesion. Conversely, transfection of MCF-7 with LOX increased cell invasiveness, migration and adhesion (reviewed in Payne et al., 2007). Focal adhesion kinase (FAK) and src kinase were decreased with bAPN treatment and increased with LOX transfection. Hydrogen peroxide, a by-product of LOX activity, was necessary for FAK activity in hypoxic cells and src activation. In addition, inhibition of LOX was associated with increased Rho activity, and decreased Rac and Cdc42 activity. LOX was determined to promote p130Cas phosphorylation and formation of the p130Cas/Crk/DOCK180 signaling complex that would increase Rac-GTP, decrease actin stress fiber formation and increase formation of lamellipodium (reviewed in Payne et al., 2007). Intense staining of extracellular LOX was observed at the leading edge of MDA-MB-231 cells grown on collagen, localizing along the hairlike fibers protruding from the cell surface, accompanied by remodeling of the actin cytoskeleton, and increased formation of stress fibers and focal adhesion (Erler et al., 2006). Cell migration may also be influenced by the interaction of LOX with placental lactogen (Polgar et al., 2007), a protein implicated in breast cancer and associated with increased incidence of lymph node metastases (Latham et al., 2001). Cell invasion, migration and adhesion may also involve interaction between LOX and fibronectin (Fogelgren et al., 2005). LOX mRNA expression was determined to be regulated by HIF-1 through a hypoxia-responsive element in the LOX promoter. Increased LOX expression was found in hypoxic patients, and was associated with negative estrogen receptor status (ER-), decreased overall survival in ER- patients and node-negative patients who did not receive adjuvant systemic treatment, and shorter metastasis-free survival in ER- patients and node negative patients (Erler et al., 2006; Helleman et al., 2008). Another study found LOX expression to only correlate with tumor hypoxia in primary breast cancers, thus LOX expression may not be stimulated by hypoxia in later stages of tumor progression (Postovit et al., 2008). Intratumoral administration of bAPN resulted in growth inhibition of tumors formed by orthotopic injection of the 13 762NF cell line into rats (reviewed in Chvapil, 2005). Orthotopic injection of either MDA-MB-231 cells transfected with LOX shRNA, or MDA-MB-231 cells followed by treatment with bAPN or LOX antibody (which also inhibited LOX activity), demonstrated fewer or no lung metastasis, respectively, and no liver metastasis. Increased in vitro invasive ability of MDA-MB-231 under hypoxic/anoxic conditions, was repressed by inhibition of extracellular catalytically active LOX by treatment with LOX antisense oligos, bAPN, LOX antibody, LOX shRNA or an extracellular copper chelator (Erler et al., 2006). In an computational model of oxidative stress in vascular smooth muscle cells, lysyl hydroxylase, syk tyrosine kinase and osteopontin, markers of breast cancer cell growth, migration, invasion and metastases, were identified as behavioral predictors of lysyl oxidase (Johnson et al., 2007). |
| Entity | Cervical cancer |
| Note | SiHa cervical cancer cells demonstrated increased invasion in vitro under hypoxic/anoxic conditions, that was repressed by inhibition of extracellular catalytically active LOX by treatment with LOX antisense oligos, bAPN, LOX antibody, LOX shRNA or an extracellular copper chelator (Erler et al., 2006). |
| Entity | Choriocarcinoma |
| Note | Choriocarcinoma cell lines BeWo and JEG-3 had decreased levels of lysyl oxidase activity (Kuivaniemi et al., 1986). JEG-3 was also shown to have decreased LOX mRNA expression (Hamalainen et al., 1995). |
| Entity | Colon cancer |
| Note | Reduced LOX mRNA levels were described in a colon cancer cell line panel, two of which (HCT-116, Colo205) demonstrated complete methylation of the LOX promoter and loss of LOX expression. Treatment of HCT-116 cells with 5-aza-dC induced gain of LOX expression (Kaneda et al., 2004). Significant loss of heterozygosity or allelic imbalance was reported in colon cancer, and a panel of colon cancer samples was noted to have reduced LOX mRNA levels. Somatic mutations emcompassing one nonsense mutation that affected codon 332, a 3' rearrangement affecting exons 5-7, and six 5' intragenic alterations or deletions, were detected out of the 8 colon tumors that demonstrated both loss of heterozygosity and reduced LOX expression (Csiszar et al., 2002). |
| Entity | Esophageal cancer |
| Note | Reduced lysyl oxidase mRNA expression was observed in esophageal cancers, and was further reduced in tumors with lymph node metastasis (He et al., 2002). |
| Entity | Fibrosarcoma |
| Note | Fibrosarcoma cell lines 8387 and HT-1080 had decreased levels of lysyl oxidase activity (Kuivaniemi et al., 1986). HT-1080 was also shown to have decreased LOX mRNA expression (Hamalainen et al., 1995). |
| Entity | Gastric cancer |
| Note | Reduced expression rate of lysyl oxidase mRNA was observed in gastric cardiac and gastric cancers, and was further reduced in tumors with lymph node metastasis (He et al., 2002). Reduced LOX mRNA expression was described in a gastric cancer cell line panel, four of which (KATOIII, MKN28, MKN74, AGS) demonstrated complete methylation of the LOX promoter and loss of LOX expression which was reversed upon treatment with 5-aza-dC. Transfection of LOX into the gastric cancer cell lines, MKN28 and KATOIII, resulted in decreased numbers of colonies in soft agar, reduced number of anchorage-dependent colonies, and smaller tumors after injection into nude mice (Kaneda et al., 2004). |
| Entity | Head and neck squamous cell carcinoma (HNSCC) |
| Note | Reduced LOX mRNA levels were noted in HNSCC cell lines and tissues. In the tissues, there was also a negative correlation between LOX levels and UICC- or T-stage of the tumor (Rost et al., 2003). In oral squamous cell carcinoma cultured cells, LOX expression was highest in precancerous lesions. LOX overexpression induced reduced migration and invasion, with lower LOX expression associated with increased neck lymph node metastasis (Shieh et al., 2007). Increased levels of LOX protein were distributed in the stromal reactions of squamous cell carcinomas, directly adjacent to invading epithelial cells. The increased expression was less than the up-regulation seen in oral submucous fibrosis (Trivedy et al., 1999). In oral squamous cell carcinoma, LOX mRNA expression was upregulated compared to normal mucosa (Ziober et al., 2006). In head and neck squamous cell carcinomas, increased LOX expression was found in association with CA-IX, a marker of hypoxia, and was associated with decreased cancer specific survival, decreased overall survival and lower metastasis-free survival (Erler et al., 2006; Le et al., 2007). |
| Entity | Lung cancer |
| Note | Reduced LOX mRNA expression was described in a lung cancer cell line panel, one of which (VRMC-LCD) demonstrated complete methylation of the LOX promoter and loss of LOX expression which was reversed upon treatment with 5-aza-dC (Kaneda et al., 2004). The epigenetic modulation of LOX was supported by the induction of LOX expression by 5-aza-dC in non-small cell lung cancer cell lines (Shames et al., 2006). In bronchogenic carcinoma tissues, LOX mRNA expression levels in Stage I, II and IV were 161%, 83% and 47% of normal adjacent lung tissue, respectively, with a similar pattern of reduction in LOX protein expression (Woznick et al., 2005). Microarray analysis demonstrated decreased LOX mRNA expression in primary lung adenocarcinoma tissues and lung cancer cell lines compared to normal lung tissues and lung cells (Wu et al., 2007). In the fibrous stromal reaction typically seen in non-small cell adenocarcinoma, strong LOX expression was observed with the fibrillar reaction (mainly collagens type I and III, fibronectin and elastic fibers), and discriminated the tumor-stroma interface of late densely organized desmoplasia. In the microfibrillar angiogenic stromal reaction seen with small cell carcinoma and neuroendocrine carcinoma, there was slight LOX expression, co-localized with type I collagen that was a minor component of the stroma (mainly laminin and fibrillin), and increased LOX expression in the thickened alveolar septa adjacent to the progression front. In the pseudostromal reaction seen with non-sclerosing broncho-alveolar carcinoma, LOX stained the thickened septa (fibronectin and numerous elastic fibers) edged by tumor cells (Peyrol et al., 2000). Repression of TGFbRII by siRNA in the lung carcinoma cell line H23, was associated with increased number of invasive cells and increased levels of LOX mRNA (Borczuk et al., 2005). |
| Entity | Melanoma |
| Note | The melanoma cell line G-361 had decreased levels of lysyl oxidase activity (Kuivaniemi et al., 1986). LOX mRNA expression was demonstrated to be absent in poorly invasive cutaneous and uveal melanoma cell lines (A375P and OCM-1A), and highly expressed in highly invasive cutaneous and uveal melanoma cell lines (C8161, M619, C918) (Kirschmann et al., 2002). B16F-10 melanoma cells treated with beta-carotene had decreased LOX mRNA expression, and with Biophytum sensitivum or amentoflavone had decreased motility, invasion, in vivo metastasis and decreased LOX mRNA expression in lung metastases (Guruvayoorappan and Kuttan, 2007; Guruvayoorappan and Kuttan, 2008; Guruvayoorappan and Kuttan, 2008). |
| Entity | Multiple endocrine neoplasia (MEN) |
| Note | Lysyl oxidase mRNA expression was repressed in NIH 3T3 cells expressing either RET-MEN2A or RET-MEN2B mutant proteins (Watanabe et al., 2002). |
| Entity | Ovarian cancer |
| Note | Evaluation of an ovarian cancer cell line panel revealed reduced LOX mRNA levels, three of which (RMUG-L, RTSG, TYK-nu) demonstrated complete methylation of the LOX promoter and loss of LOX expression (Kaneda et al., 2004). |
| Entity | Pancreatic cancer |
| Note | Reduced levels of LOX mRNA was noted in a pancreatic cancer cell line panel (Kaneda et al., 2004). Microarray analysis demonstrated decreased LOX mRNA expression in primary pancreatic tumor tissues and cell lines compared to normal pancreatic tissues and cultured cells (Wu et al., 2007). |
| Entity | Prostate cancer |
| Note | LOX was detected by differential display PCR in primary vs. metastatic prostate cancer cells following TGF-b1 stimulation. LOX was detectable in more primary prostate tumor-derived cell lines than metastasis-derived cell lines, indicating that reduced LOX mRNA levels may be an acquired feature of the metastatic phenotype in cultured cells. Immunohistochemistry showed progressive reduction of lysyl oxidase expression with the transition from normal prostate epithelium to malignant prostate epithelium to metastatic tumors in both human and mouse tissues (Ren et al., 1998). LOX mRNA expression was demonstrated to be absent in a poorly invasive rat prostate cancer cell line, compared to highly invasive rat prostate cancer cell lines (Kirschmann et al., 2002). In tissues, LOX mRNA was upregulated in prostate cancer compared to benign prostatic hypertrophy, correlated with Gleason score, and associated with both high grade and short time to recurrence (Lapointe et al., 2004; Stewart et al., 2008). LOX mRNA is upregulated in the PC-3 prostate cancer cell line cultured under hypoxic conditions (Stewart et al., 2009). |
| Entity | Renal cell carcinoma (RCC) |
| Note | Up-regulation of LOX mRNA expression was detected in RCC cell lines and tissues (Ross et al., 2000; Stassar et al., 2001). Clear cell RCC also demonstrated LOX up-regulation (Takahashi et al., 2001). Indeed, LOX overexpression appeared preferentially in clear cell RCC compared to mixed clear and granular, granular, oxyphil, tubulopapillary, and chromophobe RCC/ontocytomas (Stassar et al., 2001; Young et al., 2001). In clear cell RCC, smoking was associated with allelic imbalances at chromosome 5q23.1, where the LOX gene is localized, and may involve duplication of the gene (Korenaga et al., 2005). |
| Entity | Rhabdomyosarcoma |
| Note | Rhabdomyosarcoma cell lines RD and A-204 had decreased levels of lysyl oxidase activity (Kuivaniemi et al., 1986). RD was also shown to have decreased LOX mRNA expression (Hamalainen et al., 1995). |
| Breakpoints |
| Note | None involving the LOX gene. |
| Bibliography |
| Induction of lung lysyl oxidase activity and lysyl oxidase protein by exposure of rats to cadmium chloride: properties of the induced enzyme. |
| Almassian B, Trackman PC, Iguchi H, Boak A, Calvaresi D, Kagan HM. |
| Connect Tissue Res. 1991;25(3-4):197-208. |
| PMID 1676359 |
| A novel 2D-based approach to the discovery of candidate substrates for the metalloendopeptidase meprin. |
| Ambort D, Stalder D, Lottaz D, Huguenin M, Oneda B, Heller M, Sterchi EE. |
| FEBS J. 2008 Sep;275(18):4490-509. Epub 2008 Jul 30. |
| PMID 18671728 |
| Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis. |
| Anderson C, Bartlett SJ, Gansner JM, Wilson D, He L, Gitlin JD, Kelsh RN, Dowden J. |
| Mol Biosyst. 2007 Jan;3(1):51-9. Epub 2006 Nov 14. |
| PMID 17216056 |
| Quinoprotein-catalysed reactions. |
| Anthony C. |
| Biochem J. 1996 Dec 15;320 ( Pt 3):697-711. Review |
| PMID 9003352 |
| Cartilage growth and remodeling: modulation of balance between proteoglycan and collagen network in vitro with beta-aminopropionitrile. |
| Asanbaeva A, Masuda K, Thonar EJ, Klisch SM, Sah RL. |
| Osteoarthritis Cartilage. 2008 Jan;16(1):1-11. Epub 2007 Jul 16. |
| PMID 17631390 |
| Lysyl oxidase binds transforming growth factor-beta and regulates its signaling via amine oxidase activity. |
| Atsawasuwan P, Mochida Y, Katafuchi M, Kaku M, Fong KS, Csiszar K, Yamauchi M. |
| J Biol Chem. 2008 Dec 5;283(49):34229-40. Epub 2008 Oct 2. |
| PMID 18835815 |
| Influence of microvascular endothelial cells on transcriptional regulation of proximal tubular epithelial cells. |
| Aydin S, Signorelli S, Lechleitner T, Joannidis M, Pleban C, Perco P, Pfaller W, Jennings P. |
| Am J Physiol Cell Physiol. 2008 Feb;294(2):C543-54. Epub 2007 Dec 5. |
| PMID 18057119 |
| Structural design and molecular evolution of a cytokine receptor superfamily. |
| Bazan JF. |
| Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934-8. |
| PMID 2169613 |
| Dysregulation of pulmonary elastin synthesis and assembly in preterm lambs with chronic lung disease. |
| Bland RD, Xu L, Ertsey R, Rabinovitch M, Albertine KH, Wynn KA, Kumar VH, Ryan RM, Swartz DD, Csiszar K, Fong KS. |
| Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1370-84. Epub 2007 Feb 9. |
| PMID 17293375 |
| Lung adenocarcinoma global profiling identifies type II transforming growth factor-beta receptor as a repressor of invasiveness. |
| Borczuk AC, Kim HK, Yegen HA, Friedman RA, Powell CA. |
| Am J Respir Crit Care Med. 2005 Sep 15;172(6):729-37. Epub 2005 Jun 23. |
| PMID 15976377 |
| The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model. |
| Bouez C, Reynaud C, Noblesse E, Thepot A, Gleyzal C, Kanitakis J, Perrier E, Damour O, Sommer P. |
| Clin Cancer Res. 2006 Mar 1;12(5):1463-9. |
| PMID 16533769 |
| The size heterogeneity of human lysyl oxidase mRNA is due to alternate polyadenylation site and not alternate exon usage. |
| Boyd CD, Mariani TJ, Kim Y, Csiszar K. |
| Mol Biol Rep. 1995;21(2):95-103. |
| PMID 8531927 |
| Lysyl oxidase (LOX) mRNA expression and genes of the differentiated osteoblastic phenotype are upregulated in human osteosarcoma cells by suramin. |
| Buchinger B, Spitzer S, Karlic H, Klaushofer K, Varga F. |
| Cancer Lett. 2008 Jun 28;265(1):45-54. Epub 2008 Apr 18. |
| PMID 18374478 |
| The role of lysyl oxidase and collagen crosslinking during sea urchin development. |
| Butler E, Hardin J, Benson S. |
| Exp Cell Res. 1987 Nov;173(1):174-82. |
| PMID 2890532 |
| Downregulation of lysyl oxidase and upregulation of cellular thiols in rat fetal lung fibroblasts treated with cigarette smoke condensate. |
| Chen LJ, Zhao Y, Gao S, Chou IN, Toselli P, Stone P, Li W. |
| Toxicol Sci. 2005 Feb;83(2):372-9. Epub 2004 Oct 27. |
| PMID 15509664 |
| Inhibition of breast adenocarcinoma growth by intratumoral injection of lipophilic long-acting lathyrogens. |
| Chvapil M. |
| Anticancer Drugs. 2005 Feb;16(2):201-10. |
| PMID 15655419 |
| Epigenetic inhibition of lysyl oxidase transcription after transformation by ras oncogene. |
| Contente S, Kenyon K, Sriraman P, Subramanyan S, Friedman RM. |
| Mol Cell Biochem. 1999 Apr;194(1-2):79-91. |
| PMID 10391127 |
| Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment. |
| Coral K, Angayarkanni N, Madhavan J, Bharathselvi M, Ramakrishnan S, Nandi K, Rishi P, Kasinathan N, Krishnakumar S. |
| Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4746-52. Epub 2008 Jun 19. |
| PMID 18566459 |
| Collagen lysyl oxidase activity in the lung increases during bleomycin-induced lung fibrosis. |
| Counts DF, Evans JN, Dipetrillo TA, Sterling KM Jr, Kelley J. |
| J Pharmacol Exp Ther. 1981 Dec;219(3):675-8. |
| PMID 6170751 |
| The proteolytic processing site of the precursor of lysyl oxidase. |
| Cronshaw AD, Fothergill-Gilmore LA, Hulmes DJ. |
| Biochem J. 1995 Feb 15;306 ( Pt 1):279-84. |
| PMID 7864821 |
| Functional analysis of the promoter and first intron of the human lysyl oxidase gene. |
| Csiszar K, Entersz I, Trackman PC, Samid D, Boyd CD. |
| Mol Biol Rep. 1996;23(2):97-108. |
| PMID 8983023 |
| Somatic mutations of the lysyl oxidase gene on chromosome 5q23.1 in colorectal tumors. |
| Csiszar K, Fong SF, Ujfalusi A, Krawetz SA, Salvati EP, Mackenzie JW, Boyd CD. |
| Int J Cancer. 2002 Feb 10;97(5):636-42. |
| PMID 11807790 |
| A restriction fragment length polymorphism results in a nonconservative amino acid substitution encoded within the first exon of the human lysyl oxidase gene. |
| Csiszar K, Mariani TJ, Gosin JS, Deak SB, Boyd CD. |
| Genomics. 1993 May;16(2):401-6. |
| PMID 8100215 |
| Lysyl oxidases: a novel multifunctional amine oxidase family. |
| Csiszar K. |
| Prog Nucleic Acid Res Mol Biol. 2001;70:1-32. Review |
| PMID 11642359 |
| MicroRNAs and the hallmarks of cancer. |
| Dalmay T, Edwards DR. |
| Oncogene. 2006 Oct 9;25(46):6170-5. Review |
| PMID 17028596 |
| Micro-injection of recombinant lysyl oxidase blocks oncogenic p21-Ha-Ras and progesterone effects on Xenopus laevis oocyte maturation. |
| Di Donato A, Lacal JC, Di Duca M, Giampuzzi M, Ghiggeri G, Gusmano R. |
| FEBS Lett. 1997 Dec 8;419(1):63-8. |
| PMID 9426221 |
| Retinoic acid prevents downregulation of ras recision gene/lysyl oxidase early in adipocyte differentiation. |
| Dimaculangan DD, Chawla A, Boak A, Kagan HM, Lazar MA. |
| Differentiation. 1994 Nov;58(1):47-52. |
| PMID 7867896 |
| Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. |
| Drewes PG, Yanagisawa H, Starcher B, Hornstra I, Csiszar K, Marinis SI, Keller P, Word RA. |
| Am J Pathol. 2007 Feb;170(2):578-89. |
| PMID 17255326 |
| Lysyl oxidase is essential for hypoxia-induced metastasis. |
| Erler JT, Bennewith KL, Nicolau M, Dornhofer N, Kong C, Le QT, Chi JT, Jeffrey SS, Giaccia AJ. |
| Nature. 2006 Apr 27;440(7088):1222-6. |
| PMID 16642001 |
| Cellular fibronectin binds to lysyl oxidase with high affinity and is critical for its proteolytic activation. |
| Fogelgren B, Polgar N, Szauter KM, Ujfaludi Z, Laczko R, Fong KS, Csiszar K. |
| J Biol Chem. 2005 Jul 1;280(26):24690-7. Epub 2005 Apr 19. |
| PMID 15843371 |
| Gene expression profiling of gliomas strongly predicts survival. |
| Freije WA, Castro-Vargas FE, Fang Z, Horvath S, Cloughesy T, Liau LM, Mischel PS, Nelson SF. |
| Cancer Res. 2004 Sep 15;64(18):6503-10. |
| PMID 15374961 |
| Reversion by deletion of transforming oncogene following interferon-beta and retinoic acid treatment. |
| Friedman RM, Yeh A, Gutman P, Contente S, Kenyon K. |
| J Interferon Cytokine Res. 1997 Oct;17(10):647-51. |
| PMID 9355967 |
| Identification of differentially expressed genes by mutually subtracted RNA fingerprinting. |
| Fuchs B, Zhang K, Bolander ME, Sarkar G. |
| Anal Biochem. 2000 Nov 1;286(1):91-8. |
| PMID 11038279 |
| Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis. |
| Gansner JM, Madsen EC, Mecham RP, Gitlin JD. |
| Dev Dyn. 2008 Oct;237(10):2844-61. |
| PMID 18816837 |
| Transcriptional and posttranscriptional inhibition of lysyl oxidase expression by cigarette smoke condensate in cultured rat fetal lung fibroblasts. |
| Gao S, Chen K, Zhao Y, Rich CB, Chen L, Li SJ, Toselli P, Stone P, Li W. |
| Toxicol Sci. 2005 Sep;87(1):197-203. Epub 2005 Jun 2. |
| PMID 15933228 |
| Cloning and characterization of the rat lysyl oxidase gene promoter: identification of core promoter elements and functional nuclear factor I-binding sites. |
| Gao S, Zhao Y, Kong L, Toselli P, Chou IN, Stone P, Li W. |
| J Biol Chem. 2007 Aug 31;282(35):25322-37. Epub 2007 Jun 27. |
| PMID 17597074 |
| Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. |
| Georges PC, Hui JJ, Gombos Z, McCormick ME, Wang AY, Uemura M, Mick R, Janmey PA, Furth EE, Wells RG. |
| Am J Physiol Gastrointest Liver Physiol. 2007 Dec;293(6):G1147-54. Epub 2007 Oct 11. |
| PMID 17932231 |
| beta-catenin signaling and regulation of cyclin D1 promoter in NRK-49F cells transformed by down-regulation of the tumor suppressor lysyl oxidase. |
| Giampuzzi M, Oleggini R, Albanese C, Pestell R, Di Donato A. |
| Biochim Biophys Acta. 2005 Sep 30;1745(3):370-81. |
| PMID 15946752 |
| Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer's disease brain. |
| Gilad GM, Kagan HM, Gilad VH. |
| Neurosci Lett. 2005 Mar 16;376(3):210-4. Epub 2004 Dec 15. |
| PMID 15721223 |
| Transforming growth factor-beta1 mediated up-regulation of lysyl oxidase in the kidneys of hereditary nephrotic mouse with chronic renal fibrosis. |
| Goto Y, Uchio-Yamada K, Anan S, Yamamoto Y, Ogura A, Manabe N. |
| Virchows Arch. 2005 Nov;447(5):859-68. Epub 2005 Aug 5. |
| PMID 16086153 |
| Intracellular distribution of the lysyl oxidase propeptide in osteoblastic cells. |
| Guo Y, Pischon N, Palamakumbura AH, Trackman PC. |
| Am J Physiol Cell Physiol. 2007 Jun;292(6):C2095-102. Epub 2007 Feb 7. |
| PMID 17287363 |
| Amentoflavone inhibits experimental tumor metastasis through a regulatory mechanism involving MMP-2, MMP-9, prolyl hydroxylase, lysyl oxidase, VEGF, ERK-1, ERK-2, STAT-1, nm23 and cytokines in lung tissues of C57BL/6 mice. |
| Guruvayoorappan C, Kuttan G. |
| Immunopharmacol Immunotoxicol. 2008;30(4):711-27. |
| PMID 18686102 |
| Up-regulation of lysyl oxidase in spontaneous revertants of H-ras-transformed rat fibroblasts. |
| Hajnal A, Klemenz R, Schafer R. |
| Cancer Res. 1993 Oct 1;53(19):4670-5. |
| PMID 7691400 |
| Quantitative polymerase chain reaction of lysyl oxidase mRNA in malignantly transformed human cell lines demonstrates that their low lysyl oxidase activity is due to low quantities of its mRNA and low levels of transcription of the respective gene. |
| Hamalainen ER, Kemppainen R, Kuivaniemi H, Tromp G, Vaheri A, Pihlajaniemi T, Kivirikko KI. |
| J Biol Chem. 1995 Sep 15;270(37):21590-3. |
| PMID 7665572 |
| Lysyl oxidase gene expression and enzyme activity in the rat ovary: regulation by follicle-stimulating hormone, androgen, and transforming growth factor-beta superfamily members in vitro. |
| Harlow CR, Rae M, Davidson L, Trackman PC, Hillier SG. |
| Endocrinology. 2003 Jan;144(1):154-62. |
| PMID 12488341 |
| Use of an in vitro model of tissue-engineered skin to investigate the mechanism of skin graft contraction. |
| Harrison CA, Gossiel F, Layton CM, Bullock AJ, Johnson T, Blumsohn A, MacNeil S. |
| Tissue Eng. 2006 Nov;12(11):3119-33. |
| PMID 17518627 |
| Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: changes in the expression of LOXL during development and growth of mouse tissues. |
| Hayashi K, Fong KS, Mercier F, Boyd CD, Csiszar K, Hayashi M. |
| J Mol Histol. 2004 Nov;35(8-9):845-55. |
| PMID 15609098 |
| [Expression of lysyl oxidase gene in upper digestive tract carcinomas and its clinical significance] |
| He J, Tang HJ, Wang YY, Xiong MH, Zhou F, Shao K, Li TP. |
| Ai Zheng. 2002 Jun;21(6):671-4. |
| PMID 12452073 |
| Association of an extracellular matrix gene cluster with breast cancer prognosis and endocrine therapy response. |
| Helleman J, Jansen MP, Ruigrok-Ritstier K, van Staveren IL, Look MP, Meijer-van Gelder ME, Sieuwerts AM, Klijn JG, Sleijfer S, Foekens JA, Berns EM. |
| Clin Cancer Res. 2008 Sep 1;14(17):5555-64. |
| PMID 18765548 |
| Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. |
| Higgins DF, Kimura K, Bernhardt WM, Shrimanker N, Akai Y, Hohenstein B, Saito Y, Johnson RS, Kretzler M, Cohen CD, Eckardt KU, Iwano M, Haase VH. |
| J Clin Invest. 2007 Dec;117(12):3810-20. |
| PMID 18037992 |
| Lysyl oxidase is required for vascular and diaphragmatic development in mice. |
| Hornstra IK, Birge S, Starcher B, Bailey AJ, Mecham RP, Shapiro SD. |
| J Biol Chem. 2003 Apr 18;278(16):14387-93. Epub 2002 Dec 7. |
| PMID 12473682 |
| Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation. |
| Hurtado PA, Vora S, Sume SS, Yang D, St Hilaire C, Guo Y, Palamakumbura AH, Schreiber BM, Ravid K, Trackman PC. |
| Biochem Biophys Res Commun. 2008 Feb 1;366(1):156-61. Epub 2007 Dec 3. |
| PMID 18060869 |
| Occlusal hypofunction induces atrophic changes in rat gingiva. |
| Ishida Y, Kanno Z, Soma K. |
| Angle Orthod. 2008 Nov;78(6):1015-22. |
| PMID 18947276 |
| Intracellular localization of the matrix enzyme lysyl oxidase in polarized epithelial cells. |
| Jansen MK, Csiszar K. |
| Matrix Biol. 2007 Mar;26(2):136-9. Epub 2006 Sep 19. |
| PMID 17074474 |
| Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B. |
| Jeay S, Pianetti S, Kagan HM, Sonenshein GE. |
| Mol Cell Biol. 2003 Apr;23(7):2251-63. |
| PMID 12640111 |
| Insight into redox-regulated gene networks in vascular cells. |
| Johnson CD, Balagurunathan Y, Dougherty ER, Afshari CA, He Q, Ramos KS. |
| Bioinformation. 2007 Apr 10;1(10):379-83. |
| PMID 17597926 |
| Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. |
| Kagan HM, Li W. |
| J Cell Biochem. 2003 Mar 1;88(4):660-72. Review |
| PMID 12577300 |
| Properties and function of lysyl oxidase. |
| Kagan HM, Trackman PC. |
| Am J Respir Cell Mol Biol. 1991 Sep;5(3):206-10. Review |
| PMID 1680355 |
| Histone H1 is a substrate for lysyl oxidase and contains endogenous sodium borotritide-reducible residues. |
| Kagan HM, Williams MA, Calaman SD, Berkowitz EM. |
| Biochem Biophys Res Commun. 1983 Aug 30;115(1):186-92. |
| PMID 6137217 |
| Lysyl oxidase: mechanism, regulation and relationship to liver fibrosis. |
| Kagan HM. |
| Pathol Res Pract. 1994 Oct;190(9-10):910-9. Review |
| PMID 7899140 |
| Post-translational modifications of collagen upon BMP-induced osteoblast differentiation. |
| Kaku M, Mochida Y, Atsawasuwan P, Parisuthiman D, Yamauchi M. |
| Biochem Biophys Res Commun. 2007 Aug 3;359(3):463-8. Epub 2007 May 25. |
| PMID 17553463 |
| Identification of silencing of nine genes in human gastric cancers. |
| Kaneda A, Kaminishi M, Yanagihara K, Sugimura T, Ushijima T. |
| Cancer Res. 2002 Nov 15;62(22):6645-50. |
| PMID 12438262 |
| Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers. |
| Kaneda A, Wakazono K, Tsukamoto T, Watanabe N, Yagi Y, Tatematsu M, Kaminishi M, Sugimura T, Ushijima T. |
| Cancer Res. 2004 Sep 15;64(18):6410-5. |
| PMID 15374948 |
| Hydroxypyridinium collagen crosslinks in serum, urine, synovial fluid and synovial tissue in patients with rheumatoid arthritis compared with osteoarthritis. |
| Kaufmann J, Mueller A, Voigt A, Carl HD, Gursche A, Zacher J, Stein G, Hein G. |
| Rheumatology (Oxford). 2003 Feb;42(2):314-20. |
| PMID 12595629 |
| Lysyl oxidase and rrg messenger RNA. |
| Kenyon K, Contente S, Trackman PC, Tang J, Kagan HM, Friedman RM. |
| Science. 1991 Aug 16;253(5021):802. |
| PMID 1678898 |
| Bone morphogenetic protein-1: the type I procollagen C-proteinase. |
| Kessler E, Takahara K, Biniaminov L, Brusel M, Greenspan DS. |
| Science. 1996 Jan 19;271(5247):360-2. |
| PMID 8553073 |
| A molecular role for lysyl oxidase in breast cancer invasion. |
| Kirschmann DA, Seftor EA, Fong SF, Nieva DR, Sullivan CM, Edwards EM, Sommer P, Csiszar K, Hendrix MJ. |
| Cancer Res. 2002 Aug 1;62(15):4478-83. |
| PMID 12154058 |
| Decreased endopelvic fascia elastin content in uterine prolapse. |
| Klutke J, Ji Q, Campeau J, Starcher B, Felix JC, Stanczyk FZ, Klutke C. |
| Acta Obstet Gynecol Scand. 2008;87(1):111-5. |
| PMID 18158636 |
| Immunohistochemical localization of lysyl oxidase in normal human skin. |
| Kobayashi H, Ishii M, Chanoki M, Yashiro N, Fushida H, Fukai K, Kono T, Hamada T, Wakasaki H, Ooshima A. |
| Br J Dermatol. 1994 Sep;131(3):325-30. |
| PMID 7918005 |
| Smoking may cause genetic alterations at 5q22.2 approximately q23.1 in clear-cell renal cell carcinoma. |
| Korenaga Y, Matsuyama H, Hirata H, Nagao K, Ohmi C, Sakano S, Yoshihiro S, Naito K. |
| Cancer Genet Cytogenet. 2005 Nov;163(1):7-11. |
| PMID 16271949 |
| Incorporation of copper into lysyl oxidase. |
| Kosonen T, Uriu-Hare JY, Clegg MS, Keen CL, Rucker RB. |
| Biochem J. 1997 Oct 1;327 ( Pt 1):283-9. |
| PMID 9355764 |
| Benefits of concurrent delivery of hyaluronan and IGF-1 cues to regeneration of crosslinked elastin matrices by adult rat vascular cells. |
| Kothapalli CR, Ramamurthi A. |
| J Tissue Eng Regen Med. 2008 Mar-Apr;2(2-3):106-16. |
| PMID 18338830 |
| Lysyl oxidase copper-talon complex: a model. |
| Krebs CJ, Krawetz SA. |
| Biochim Biophys Acta. 1993 Sep 3;1202(1):7-12. |
| PMID 8104038 |
| Isolation of genes specifically expressed in flat revertant cells derived from activated ras-transformed NIH 3T3 cells by treatment with azatyrosine. |
| Krzyzosiak WJ, Shindo-Okada N, Teshima H, Nakajima K, Nishimura S. |
| Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4879-83. |
| PMID 1594588 |
| Deficient production of lysyl oxidase in cultures of malignantly transformed human cells. |
| Kuivaniemi H, Korhonen RM, Vaheri A, Kivirikko KI. |
| FEBS Lett. 1986 Jan 20;195(1-2):261-4. |
| PMID 3753686 |
| Active lysyl oxidase (LOX) correlates with focal adhesion kinase (FAK)/paxillin activation and migration in invasive astrocytes. |
| Laczko R, Szauter KM, Jansen MK, Hollosi P, Muranyi M, Molnar J, Fong KS, Hinek A, Csiszar K. |
| Neuropathol Appl Neurobiol. 2007 Dec;33(6):631-43. Epub 2007 Oct 11. |
| PMID 17931358 |
| Gene expression profiling identifies clinically relevant subtypes of prostate cancer. |
| Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR. |
| Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):811-6. Epub 2004 Jan 7. |
| PMID 14711987 |
| Frequent co-amplification of two different regions on 17q in aneuploid breast carcinomas. |
| Latham C, Zhang A, Nalbanti A, Maner S, Zickert P, Blegen H, Zetterberg A. |
| Cancer Genet Cytogenet. 2001 May;127(1):16-23. |
| PMID 11408059 |
| Induction of human monocyte motility by lysyl oxidase. |
| Lazarus HM, Cruikshank WW, Narasimhan N, Kagan HM, Center DM. |
| Matrix Biol. 1995 Dec;14(9):727-31. |
| PMID 8785587 |
| Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas. |
| Le QT, Kong C, Lavori PW, O'byrne K, Erler JT, Huang X, Chen Y, Cao H, Tibshirani R, Denko N, Giaccia AJ, Koong AC. |
| Int J Radiat Oncol Biol Phys. 2007 Sep 1;69(1):167-75. |
| PMID 17707270 |
| VE-statin/egfl7 regulates vascular elastogenesis by interacting with lysyl oxidases. |
| Lelievre E, Hinek A, Lupu F, Buquet C, Soncin F, Mattot V. |
| EMBO J. 2008 Jun 18;27(12):1658-70. Epub 2008 May 22. |
| PMID 18497746 |
| Up-regulation and altered distribution of lysyl oxidase in the central nervous system of mutant SOD1 transgenic mouse model of amyotrophic lateral sclerosis. |
| Li PA, He Q, Cao T, Yong G, Szauter KM, Fong KS, Karlsson J, Keep MF, Csiszar K. |
| Brain Res Mol Brain Res. 2004 Jan 5;120(2):115-22. |
| PMID 14741400 |
| Hydrogen peroxide-mediated, lysyl oxidase-dependent chemotaxis of vascular smooth muscle cells. |
| Li W, Liu G, Chou IN, Kagan HM. |
| J Cell Biochem. 2000 Jun 12;78(4):550-7. |
| PMID 10861852 |
| Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. |
| Li W, Nellaiappan K, Strassmaier T, Graham L, Thomas KM, Kagan HM. |
| Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12817-22. |
| PMID 9371758 |
| Lysyl oxidase oxidizes basic fibroblast growth factor and inactivates its mitogenic potential. |
| Li W, Nugent MA, Zhao Y, Chau AN, Li SJ, Chou IN, Liu G, Kagan HM. |
| J Cell Biochem. 2003 Jan 1;88(1):152-64. |
| PMID 12461785 |
| Impact of treatment on myocardial lysyl oxidase expression and collagen cross-linking in patients with heart failure. |
| Lopez B, Querejeta R, Gonzalez A, Beaumont J, Larman M, Diez J. |
| Hypertension. 2009 Feb;53(2):236-42. Epub 2008 Dec 15. |
| PMID 19075089 |
| Osteitis fibrosa is mediated by Platelet-Derived Growth Factor-A via a phosphoinositide 3-kinase-dependent signaling pathway in a rat model for chronic hyperparathyroidism. |
| Lowry MB, Lotinun S, Leontovich AA, Zhang M, Maran A, Shogren KL, Palama BK, Marley K, Iwaniec UT, Turner RT. |
| Endocrinology. 2008 Nov;149(11):5735-46. Epub 2008 Jul 17. |
| PMID 18635661 |
| Lysyl oxidase: an oxidative enzyme and effector of cell function. |
| Lucero HA, Kagan HM. |
| Cell Mol Life Sci. 2006 Oct;63(19-20):2304-16. Review |
| PMID 16909208 |
| Lysyl oxidase oxidizes cell membrane proteins and enhances the chemotactic response of vascular smooth muscle cells. |
| Lucero HA, Ravid K, Grimsby JL, Rich CB, DiCamillo SJ, Maki JM, Myllyharju J, Kagan HM. |
| J Biol Chem. 2008 Aug 29;283(35):24103-17. Epub 2008 Jun 27. |
| PMID 18586678 |
| Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice. |
| Maki JM, Rasanen J, Tikkanen H, Sormunen R, Makikallio K, Kivirikko KI, Soininen R. |
| Circulation. 2002 Nov 5;106(19):2503-9. |
| PMID 12417550 |
| Lysyl oxidase is essential for normal development and function of the respiratory system and for the integrity of elastic and collagen fibers in various tissues. |
| Maki JM, Sormunen R, Lippo S, Kaarteenaho-Wiik R, Soininen R, Myllyharju J. |
| Am J Pathol. 2005 Oct;167(4):927-36. |
| PMID 16192629 |
| Differential expression of 14 genes in amyotrophic lateral sclerosis spinal cord detected using gridded cDNA arrays. |
| Malaspina A, Kaushik N, de Belleroche J. |
| J Neurochem. 2001 Apr;77(1):132-45. |
| PMID 11279269 |
| The complete derived amino acid sequence of human lysyl oxidase and assignment of the gene to chromosome 5 (extensive sequence homology with the murine ras recision gene). |
| Mariani TJ, Trackman PC, Kagan HM, Eddy RL, Shows TB, Boyd CD, Deak SB. |
| Matrix. 1992 Jun;12(3):242-8. |
| PMID 1357535 |
| Identification of differentially secreted biomarkers using LC-MS/MS in isogenic cell lines representing a progression of breast cancer. |
| Mbeunkui F, Metge BJ, Shevde LA, Pannell LK. |
| J Proteome Res. 2007 Aug;6(8):2993-3002. Epub 2007 Jul 4. |
| PMID 17608509 |
| Modulation of ras transformation affecting chromatin supraorganization as assessed by image analysis. |
| Mello ML, Contente S, Vidal BC, Planding W, Schenck U. |
| Exp Cell Res. 1995 Oct;220(2):374-82. |
| PMID 7556446 |
| Modifications of arterial phenotype in response to amine oxidase inhibition by semicarbazide. |
| Mercier N, El Hadri K, Osborne-Pellegrin M, Nehme J, Perret C, Labat C, Regnault V, Lamaziere JM, Challande P, Lacolley P, Feve B. |
| Hypertension. 2007 Jul;50(1):234-41. Epub 2007 Apr 23. |
| PMID 17452500 |
| Analysis of gene expression patterns in systemic sclerosis fibroblasts using RNA arbitrarily primed-polymerase chain reaction for differential display. |
| Meyringer R, Neumann E, Judex M, Landthaler M, Kullmann F, Scholmerich J, Gay S, Tarner IH, Distler O, Muller-Ladner U. |
| J Rheumatol. 2007 Apr;34(4):747-53. |
| PMID 17407232 |
| The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast cancer. |
| Min C, Kirsch KH, Zhao Y, Jeay S, Palamakumbura AH, Trackman PC, Sonenshein GE. |
| Cancer Res. 2007 Feb 1;67(3):1105-12. |
| PMID 17283144 |
| Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics. |
| Nagaraja GM, Othman M, Fox BP, Alsaber R, Pellegrino CM, Zeng Y, Khanna R, Tamburini P, Swaroop A, Kandpal RP. |
| Oncogene. 2006 Apr 13;25(16):2328-38. |
| PMID 16314837 |
| Fully processed lysyl oxidase catalyst translocates from the extracellular space into nuclei of aortic smooth-muscle cells. |
| Nellaiappan K, Risitano A, Liu G, Nicklas G, Kagan HM. |
| J Cell Biochem. 2000 Sep 14;79(4):576-82. |
| PMID 10996848 |
| Partial restoration of pre-transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants. |
| Oberhuber H, Seliger B, Schafer R. |
| Mol Carcinog. 1995 Apr;12(4):198-204. |
| PMID 7727041 |
| Regulation of elastin promoter by lysyl oxidase and growth factors: cross control of lysyl oxidase on TGF-beta1 effects. |
| Oleggini R, Gastaldo N, Di Donato A. |
| Matrix Biol. 2007 Jul;26(6):494-505. Epub 2007 Feb 27. |
| PMID 17395448 |
| Regulation of the expression of lysyl oxidase mRNA in cultured rabbit retinal pigment epithelium cells. |
| Omori K, Fujiseki Y, Omori K, Suzukawa J, Inagaki C. |
| Matrix Biol. 2002 Jun;21(4):337-48. |
| PMID 12128071 |
| The propeptide domain of lysyl oxidase induces phenotypic reversion of ras-transformed cells. |
| Palamakumbura AH, Jeay S, Guo Y, Pischon N, Sommer P, Sonenshein GE, Trackman PC. |
| J Biol Chem. 2004 Sep 24;279(39):40593-600. Epub 2004 Jul 23. |
| PMID 15277520 |
| Alterations in vascular gene expression in invasive breast carcinoma. |
| Parker BS, Argani P, Cook BP, Liangfeng H, Chartrand SD, Zhang M, Saha S, Bardelli A, Jiang Y, St Martin TB, Nacht M, Teicher BA, Klinger KW, Sukumar S, Madden SL. |
| Cancer Res. 2004 Nov 1;64(21):7857-66. |
| PMID 15520192 |
| Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism. |
| Payne SL, Fogelgren B, Hess AR, Seftor EA, Wiley EL, Fong SF, Csiszar K, Hendrix MJ, Kirschmann DA. |
| Cancer Res. 2005 Dec 15;65(24):11429-36. |
| PMID 16357151 |
| Paradoxical roles for lysyl oxidases in cancer--a prospect. |
| Payne SL, Hendrix MJ, Kirschmann DA. |
| J Cell Biochem. 2007 Aug 15;101(6):1338-54. Review |
| PMID 17471532 |
| A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. |
| Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, Nieto MA, Cano A, Portillo F. |
| EMBO J. 2005 Oct 5;24(19):3446-58. Epub 2005 Aug 18. |
| PMID 16096638 |
| Selective expression of lysyl oxidase (LOX) in the stromal reactions of broncho-pulmonary carcinomas. |
| Peyrol S, Galateau-Salle F, Raccurt M, Gleyzal C, Sommer P. |
| Histol Histopathol. 2000 Oct;15(4):1127-35. |
| PMID 11005237 |
| Lysyl oxidase gene expression in the stromal reaction to in situ and invasive ductal breast carcinoma. |
| Peyrol S, Raccurt M, Gerard F, Gleyzal C, Grimaud JA, Sommer P. |
| Am J Pathol. 1997 Feb;150(2):497-507. |
| PMID 9033266 |
| Lysyl oxidase interacts with hormone placental lactogen and synergistically promotes breast epithelial cell proliferation and migration. |
| Polgar N, Fogelgren B, Shipley JM, Csiszar K. |
| J Biol Chem. 2007 Feb 2;282(5):3262-72. Epub 2006 Nov 27. |
| PMID 17130123 |
| Hypoxia/reoxygenation: a dynamic regulator of lysyl oxidase-facilitated breast cancer migration. |
| Postovit LM, Abbott DE, Payne SL, Wheaton WW, Margaryan NV, Sullivan R, Jansen MK, Csiszar K, Hendrix MJ, Kirschmann DA. |
| J Cell Biochem. 2008 Apr 1;103(5):1369-78. |
| PMID 17685448 |
| Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by microarray analysis. |
| Rae MT, Niven D, Ross A, Forster T, Lathe R, Critchley HO, Ghazal P, Hillier SG. |
| J Endocrinol. 2004 Oct;183(1):19-28. |
| PMID 15525570 |
| High levels of homocysteine inhibit lysyl oxidase (LOX) and downregulate LOX expression in vascular endothelial cells. |
| Raposo B, Rodriguez C, Martinez-Gonzalez J, Badimon L. |
| Atherosclerosis. 2004 Nov;177(1):1-8. |
| PMID 15488859 |
| Reduced lysyl oxidase messenger RNA levels in experimental and human prostate cancer. |
| Ren C, Yang G, Timme TL, Wheeler TM, Thompson TC. |
| Cancer Res. 1998 Mar 15;58(6):1285-90. |
| PMID 9515817 |
| Morpholino knockdown of lysyl oxidase impairs zebrafish development, and reflects some aspects of copper metabolism disorders. |
| Reynaud C, Baas D, Gleyzal C, Le Guellec D, Sommer P. |
| Matrix Biol. 2008 Jul;27(6):547-60. Epub 2008 Mar 26. |
| PMID 18467084 |
| Molecular profiling of a rat model of colitis: validation of known inflammatory genes and identification of novel disease-associated targets. |
| Rivera E, Flores I, Rivera E, Appleyard CB. |
| Inflamm Bowel Dis. 2006 Oct;12(10):950-66. |
| PMID 17012966 |
| Regulation of lysyl oxidase in vascular cells: lysyl oxidase as a new player in cardiovascular diseases. |
| Rodriguez C, Martinez-Gonzalez J, Raposo B, Alcudia JF, Guadall A, Badimon L. |
| Cardiovasc Res. 2008 Jul 1;79(1):7-13. Epub 2008 May 9. Review |
| PMID 18469024 |
| Systematic variation in gene expression patterns in human cancer cell lines. |
| Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D, Brown PO. |
| Nat Genet. 2000 Mar;24(3):227-35. |
| PMID 10700174 |
| Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas. |
| Rost T, Pyritz V, Rathcke IO, Gorogh T, Dunne AA, Werner JA. |
| Anticancer Res. 2003 Mar-Apr;23(2B):1565-73. |
| PMID 12820424 |
| Gene expression analysis proposes alternative pathways for the mechanism by which celecoxib selectively inhibits the growth of transformed but not normal enterocytes. |
| Sagiv E, Rozovski U, Kazanov D, Liberman E, Arber N. |
| Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6807-15. |
| PMID 18006783 |
| Notch signaling mediates hypoxia-induced tumor cell migration and invasion. |
| Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. |
| Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6392-7. Epub 2008 Apr 21. |
| PMID 18427106 |
| A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. |
| Shames DS, Girard L, Gao B, Sato M, Lewis CM, Shivapurkar N, Jiang A, Perou CM, Kim YH, Pollack JR, Fong KM, Lam CL, Wong M, Shyr Y, Nanda R, Olopade OI, Gerald W, Euhus DM, Shay JW, Gazdar AF, Minna JD. |
| PLoS Med. 2006 Dec;3(12):e486. |
| PMID 17194187 |
| Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta 1-regulated genes, one of which seems to encode a follistatin-related polypeptide. |
| Shibanuma M, Mashimo J, Mita A, Kuroki T, Nose K. |
| Eur J Biochem. 1993 Oct 1;217(1):13-9. |
| PMID 7901004 |
| Association of expression aberrances and genetic polymorphisms of lysyl oxidase with areca-associated oral tumorigenesis. |
| Shieh TM, Lin SC, Liu CJ, Chang SS, Ku TH, Chang KW. |
| Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4378-85. |
| PMID 17671119 |
| Upregulation of lysyl oxidase and MMPs during cardiac remodeling in human dilated cardiomyopathy. |
| Sivakumar P, Gupta S, Sarkar S, Sen S. |
| Mol Cell Biochem. 2008 Jan;307(1-2):159-67. Epub 2007 Sep 12. |
| PMID 17849172 |
| Differentiation-dependent expression of connective tissue growth factor and lysyl oxidase messenger ribonucleic acids in rat granulosa cells. |
| Slee RB, Hillier SG, Largue P, Harlow CR, Miele G, Clinton M. |
| Endocrinology. 2001 Mar;142(3):1082-9. |
| PMID 11181522 |
| Hypoxia induced expression of endogenous markers in vitro is highly influenced by pH. |
| Sorensen BS, Alsner J, Overgaard J, Horsman MR. |
| Radiother Oncol. 2007 Jun;83(3):362-6. Epub 2007 May 18. |
| PMID 17512623 |
| Dystrophin-deficient cardiomyopathy in mouse: expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart. |
| Spurney CF, Knoblach S, Pistilli EE, Nagaraju K, Martin GR, Hoffman EP. |
| Neuromuscul Disord. 2008 May;18(5):371-81. Epub 2008 Apr 25. |
| PMID 18440230 |
| Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. |
| Stassar MJ, Devitt G, Brosius M, Rinnab L, Prang J, Schradin T, Simon J, Petersen S, Kopp-Schneider A, Zoller M. |
| Br J Cancer. 2001 Nov 2;85(9):1372-82. |
| PMID 11720477 |
| NO-sulindac inhibits the hypoxia response of PC-3 prostate cancer cells via the Akt signalling pathway. |
| Stewart GD, Nanda J, Brown DJ, Riddick AC, Ross JA, Habib FK. |
| Int J Cancer. 2009 Jan 1;124(1):223-32. |
| PMID 18924134 |
| Lysyl oxidase in development, aging and pathologies of the skin. |
| Szauter KM, Cao T, Boyd CD, Csiszar K. |
| Pathol Biol (Paris). 2005 Sep;53(7):448-56. |
| PMID 16085123 |
| Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification. |
| Takahashi M, Rhodes DR, Furge KA, Kanayama H, Kagawa S, Haab BB, Teh BT. |
| Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9754-9. Epub 2001 Aug 7. |
| PMID 11493696 |
| Reaction of aortic lysyl oxidase with beta-aminopropionitrile. |
| Tang SS, Trackman PC, Kagan HM. |
| J Biol Chem. 1983 Apr 10;258(7):4331-8. |
| PMID 6131892 |
| Oral submucous fibrosis: review on aetiology and pathogenesis. |
| Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. |
| Oral Oncol. 2006 Jul;42(6):561-8. Epub 2005 Nov 28. Review |
| PMID 16311067 |
| Inflammation-associated lysyl oxidase protein expression in vivo, and modulation by FGF-2 plus IGF-1. |
| Trackman PC, Graham RJ, Bittner HK, Carnes DL, Gilles JA, Graves DT. |
| Histochem Cell Biol. 1998 Jul;110(1):9-14. |
| PMID 9681684 |
| The upregulation of lysyl oxidase in oral submucous fibrosis and squamous cell carcinoma. |
| Trivedy C, Warnakulasuriya KA, Hazarey VK, Tavassoli M, Sommer P, Johnson NW. |
| J Oral Pathol Med. 1999 Jul;28(6):246-51. |
| PMID 10426196 |
| Collagen cross-linking influences osteoblastic differentiation. |
| Turecek C, Fratzl-Zelman N, Rumpler M, Buchinger B, Spitzer S, Zoehrer R, Durchschlag E, Klaushofer K, Paschalis EP, Varga F. |
| Calcif Tissue Int. 2008 May;82(5):392-400. Epub 2008 May 17. |
| PMID 18488133 |
| Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis. |
| Urashima T, Zhao M, Wagner R, Fajardo G, Farahani S, Quertermous T, Bernstein D. |
| Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1351-H1368. Epub 2008 Jun 27. |
| PMID 18586894 |
| Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures. |
| Uzel MI, Scott IC, Babakhanlou-Chase H, Palamakumbura AH, Pappano WN, Hong HH, Greenspan DS, Trackman PC. |
| J Biol Chem. 2001 Jun 22;276(25):22537-43. Epub 2001 Apr 19. |
| PMID 11313359 |
| Molecular events that contribute to lysyl oxidase enzyme activity and insoluble collagen accumulation in osteosarcoma cell clones. |
| Uzel MI, Shih SD, Gross H, Kessler E, Gerstenfeld LC, Trackman PC. |
| J Bone Miner Res. 2000 Jun;15(6):1189-97. |
| PMID 10841188 |
| Immunohistochemical localization of lysyl oxidase with monoclonal antibodies. |
| Wakasaki H, Ooshima A. |
| Lab Invest. 1990 Sep;63(3):377-84. |
| PMID 1975633 |
| Characterization of gene expression induced by RET with MEN2A or MEN2B mutation. |
| Watanabe T, Ichihara M, Hashimoto M, Shimono K, Shimoyama Y, Nagasaka T, Murakumo Y, Murakami H, Sugiura H, Iwata H, Ishiguro N, Takahashi M. |
| Am J Pathol. 2002 Jul;161(1):249-56. |
| PMID 12107109 |
| Granulocyte macrophage colony-stimulating factor deficiency affects vascular elastin production and integrity of elastic lamellae. |
| Weissen-Plenz G, Eschert H, Volker W, Sindermann JR, Beissert S, Robenek H, Scheld HH, Breithardt G. |
| J Vasc Res. 2008;45(2):103-10. Epub 2007 Oct 12. |
| PMID 17934321 |
| Lysyl oxidase expression in bronchogenic carcinoma. |
| Woznick AR, Braddock AL, Dulai M, Seymour ML, Callahan RE, Welsh RJ, Chmielewski GW, Zelenock GB, Shanley CJ. |
| Am J Surg. 2005 Mar;189(3):297-301. |
| PMID 15792754 |
| Repression of BCL2 by the tumor suppressor activity of the lysyl oxidase propeptide inhibits transformed phenotype of lung and pancreatic cancer cells. |
| Wu M, Min C, Wang X, Yu Z, Kirsch KH, Trackman PC, Sonenshein GE. |
| Cancer Res. 2007 Jul 1;67(13):6278-85. |
| PMID 17616686 |
| Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase in mice. |
| Yoshimura K, Aoki H, Ikeda Y, Furutani A, Hamano K, Matsuzaki M. |
| Ann N Y Acad Sci. 2006 Nov;1085:74-81. |
| PMID 17182924 |
| Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. |
| Young AN, Amin MB, Moreno CS, Lim SD, Cohen C, Petros JA, Marshall FF, Neish AS. |
| Am J Pathol. 2001 May;158(5):1639-51. |
| PMID 11337362 |
| Secretory leukocyte protease inhibitor mediates proliferation of human endometrial epithelial cells by positive and negative regulation of growth-associated genes. |
| Zhang D, Simmen RC, Michel FJ, Zhao G, Vale-Cruz D, Simmen FA. |
| J Biol Chem. 2002 Aug 16;277(33):29999-30009. Epub 2002 May 22. |
| PMID 12023969 |
| The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells. |
| Zhao Y, Min C, Vora SR, Trackman PC, Sonenshein GE, Kirsch KH. |
| J Biol Chem. 2009 Jan 16;284(3):1385-93. Epub 2008 Nov 21. |
| PMID 19029090 |
| Identification of a gene signature for rapid screening of oral squamous cell carcinoma. |
| Ziober AF, Patel KR, Alawi F, Gimotty P, Weber RS, Feldman MM, Chalian AA, Weinstein GS, Hunt J, Ziober BL. |
| Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):5960-71. |
| PMID 17062667 |
| Citation |
| This paper should be referenced as such : |
| Fong, SFT ; Fong, KSK ; Csiszar, K |
| LOX (lysyl oxidase) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(1):15-28. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/LOXID41191ch5q23.html |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Jan 17 18:59:34 CET 2019 |
For comments and suggestions or contributions, please contact us