Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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MET proto-oncogene, receptor tyrosine kinase(MET) MET proto-oncogene, receptor tyrosine kinase(MET) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 7q31,
ENSEMBL_GENE_ID ENSG00000105976,
GENERIF_SUMMARY Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition, Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer, Met sequesters Fas, preventing apoptosis., The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met, Increased c-Met expression participates in cholangiocarcinogenesis and in the early developmental stages of intrahepatic cholangiocarcinoma., high expression seen in intermediate cells in normal and malignant prostate epithelium indicates they are prone to stromal invasion in prostate carcinoma, HGF and HGFR have an alternative role activating the via STAT3 transdution and operating on placental tissues, overall in organogenesis alteration conditions, a signal transduction cascade or cross-talk emanating from CD44 to c-Met, Overexpression of HGF/c-met appears to be a biological feedback response to the fibrotic process of systemic sclerosis., MET signaling is negatively regulated by c-Cbl which induces ubiquitination of its cytoplasmic domain., MET may be one of the long sought oncogenes controlling progression of primary cancers to metastasis., immunoexpression of hepatocyte growth factor and c-Met in the eutopic endometrium of patients with pelvic endometrioisis is possibly useful to predict greater activity of the ectopic endometrium, HGF may have a role in the pathogenesis of papillary thyroid carcinoma, Radiation stimulates HGF receptor/c-Met expression that leads to amplifying cellular response to HGF stimulation via upregulated receptor tyrosine phosphorylation and MAP kinase activity in pancreatic cancer cells., up-regulated during the in vitro recapitulation of several steps of angiogenesis; expression increased shortly after switching to angiogenic growth conditions & remained high during the first steps of angiogenesis, including cell migration & proliferation, Activation of the c-Met pathway targets the PI3K pathway in small cell lung cancer, These results indicate that overexpression of hepatocyte growth factor receptor tyrosine kinase in renal carcinoma cells participates in rapid tumor growth in vivo., Ki-ras mutations and HGF signaling cooperate to enhance tumor growth by increased duration of MAPK activation and decreased apoptosis in human carcinoma cells., Met is expressed by the majority of MM cell lines and by approximately half of the primary plasma cell neoplasms tested.The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma., Endosomal dynamics of Met determine signaling output., Autocrine and paracrine support of HGF-c-Met system attenuates degeneration of anterior horn cells in amyotrophic lateral sclerosis. Disruption of neuronal HGF-c-Met system at advanced stage accelerates cellular degeneration and cell death., Role of the HGF receptor in proliferation and invasive behavior of osteosarcoma cell lines., data define a protein kinase c-controlled traffic pathway for c-Met that operates independently of its degradative pathway, hypoxia promotes tumor invasion by sensitizing cells to hepatocyte growth factor stimulation, providing a molecular basis to explain Met overexpression in cancer, Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand, Met can be detected in the axillary fluids of patients who undergo conservative operations for breast cancer, and its expression in the axillary drainage may have potential as a prognostic factor., N-terminal domain of HGF inhibits angiogenesis not by disrupting the HGF/c-met interaction but rather by interfering with the endothelial glycosaminoglycans., Activation of c-Met in colorectal carcinoma cells leads to constitutive association of tyrosine-phosphorylated beta-catenin, hepatocyte growth factor and c-Met/HGF receptor have roles in prostate neoplasm progression, c-Met signaling has roles in scattering, angiogenesis, proliferation, enhanced cell motility, invasion, and eventual metastasis [review], These data suggest that coexpression of the MET and RON receptors confer a selective advantage to ovarian cancer cells and might promote ovarian cancer progression., C-met expression is a significant marker for tall cell variant papillary carcinoma of the thyroid gland., MUC1 and Met can be detected in the axillary fluids of patients with breast cancer; the expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor, Retroviral ribozyme transgenes targeting HGF/SF in fibroblasts or its receptor cMET in mammary cancer cells can reduce the growth of mammary cancer and associated angiogenesis by inhibiting paracrine stromal-tumor cell interactions., c-Met and HGF-SF have roles in the growth and progression of human and canine osteosarcoma, establish by deletion mutagenesis that the HGF/SF and heparin-binding sites of MET are contained within a large N-terminal domain spanning the alpha-chain (amino acids 25-307) and the first 212 amino acids of the beta-chain (amino acids 308-519), Mutation present in a notable subset of patients with oropharyngeal cancer and may interfere with radioresponsiveness., Differentially expressed in gastric cancer and intestinal metaplasia., Ser-985 phosphorylation of c-Met is bi-directionally regulated through PKC and PP2A, Data identify a DpYR motif including tyrosine(1003) as being important for the direct recruitment of the c-Cbl tyrosine kinase binding domain and for ubiquitination of the Met receptor., Results provide an explanation for cell surface receptor cross-talk involving the Met receptor and link G protein-coupled receptors and the epidermal growth factor receptor to the oncogenic potential of Met signaling in human carcinoma cells., the invasive function of Met can be independent of alpha(6)beta(4); alpha(6)beta(4) has a generic influence on the invasion of carcinoma cells that is not specific to Met, c-Met oncogene is a novel tumor rejection antigen recognized by cytotoxic T-lymphocytes and expressed on a broad variety of epithelial and hematopoietic malignant cells, Met receptor can interact with each of the three members of class B Plexins and control tumor invasive growth., Met is frequently activated in these carcinomas and may favor tumor growth, and abundance of Met expression may differently regulate cell growth, morphogenesis, and migration in response to HGF., Stat3 mediated by c-Met is frequently associated with the progression of oral squamous cell carcinoma, HGF-specific immunostaining of proliferating cholangioles in the absence of HGF RNA suggests c-Met-mediated uptake of HGF and paracrine stimulation of cholangiocellular proliferation, Compared to IOSE-29, IOSE-Ov29 and IOSE-Ov29/T4 exhibited higher levels of the HGF receptor Met and an increasing duration of ERK1/2 activation with malignant progression, in conjunction with other neoplastic properties., Results suggest that MUC20 is a novel regulator of the Met signaling cascade which has a role in suppression of the Grb2-Ras pathway., Review. The role of Met in normal human prostate epithelium, and underlying mechanisms of deregulated Met expression in localized and metastatic prostate cancer are discussed., TGF-beta1 significantly induced c-met expression in human kidney cells, which primarily took place at the gene transcriptional level., Met proto-oncogene and insulin-like growth factor binding protein 3 have roles in metastasis of well-differentiated pancreatic endocrine neoplasms, K48R-linked polyubiquitin is required for Met endosomal trafficking, The autocrine mechanism between over-expressed c-Met and HGF/SF in malignant tumors is part of the process of pleural metastatic spread., These results indicate that c-Met is actually activated in gastric carcinoma tissue, and may trigger proliferation/anti-apoptotic signals., findings expand our understanding of tumor promoter/suppressor inter-relationships and downstream transcriptional effects of PTEN loss and c-Met overexpression in malignant gliomas, mutated in papillary renal cell carcinoma., The role of HGFR signal in colon tumorigenesis is associated to progression of adenoma into carcinoma., role of coreceptor for adeno-associated virus type 2 (AAV2) infection by facilitating AAV2 internalization into the cytoplasm, demonstrate that Sema4D is angiogenic in vitro and in vivo and that this effect is mediated by its high-affinity receptor, Plexin B1, and that biologic effects elicited by Plexin B1 require coupling and activation of the Met tyrosine kinase, in chronic skin ulcers, decreased biological activity of endogenous HGF and overexpression of c-met may have roles in fibrosis and delayed recovery, overexpression of c-Met is associated with advanced stage colorectal cancer, Cell proliferation, invasion, and morphological characteristics may be induced independently from the HGF/SF-Met pathway in C31/Tag metastatic prostate cancer cells., Through promoting Met-Integrin association, HGF-FN and HGF-VN complexes coordinated and enhanced endothelial cell migration through activation of the PI-3 kinase pathway involving a Ras-dependent mechanism, c-Met is overexpressed in esophageal adenocarcinoma., HGF/MET signalling protects Plasmodium sporozoite-infected host cells from apoptosis., Targeting the activated, human MET oncogene to adult mouse liver caused slowly progressing hepatocarcinogenesis, Analysis with phospho-specific antibodies indicates that 3 kinases generate a signal-specific, combinatorial phosphorylation profile of the Hrs-STAM complex, with the potential of diversifying tyrosine kinase receptor signalling through a common element., IGF-I and HGF cooperate to induce migration and invasion of colorectal carcinoma cells, and c-Met and uPA/uPAR are required for IGF-I-mediated migration and invasion., negative feedback regulation in which Met activation leads to transcriptional induction of Notch function, which in turn limits HGF activity through repression of the Met oncogene, cMet/Fas interaction may inhibit self-association of Fas receptor such that reduced DISC formation occurs in these cells after Fas receptor ligation. cMet/Fas interaction may help explain why endothelial cells are resistant to Fas-mediated apoptosis., Deregulation of the interaction between HGF and its receptor c-met during placentation may be the cause responsible for the growth retardation of the fetus due to the impaired placental functions., It is concluded that level and duration of MAPK activation by Met receptor are crucial for the induction of a full HGF-dependent mitogenic and invasive program in KS cells., Induction of Met expression by low-oxygen tension may play an important role in the physiology of early pregnancy by promoting the invasion of trophoblast cells into the decidua of the uterus., These results suggest that CD151 forms a structural and functional complex with c-Met and integrin alpha3/alpha6, and exerts its oncogenic functions through excessive activation of the HGF/c-Met signalling pathway., hepatocyte growth factor signaling and Ki-ras oncogene activation have roles in colorectal cancer, upregulation of the MET pathway may contribute to the poor outcome of esophageal adenocarcinoma patients and that therapeutic agents targeting this pathway may help improve patient survival, HGFR signaling mediates the anti-fibrotic action of alitretinoin in glomerular mesangial cells., expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema, XIAP expression in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling, using RT-PCR for the detection of c-Met or mucin 1 mRNA may be a promising tool for the early detection of micro-metastatic circulating tumor cells in gastric carcinoma patients, study showed that c-Met overexpression may be important for the progression of cervical adenocarcinomas, c-Met expression is regulated by Mitf in the melanocyte lineage, The consistent expression of HGF and c-met during the perinatal period supports a physiological role for HGF in human lung development., crystal structure, at 2.15-A resolution, of the autoinhibited form of the kinase domain, revealing an intricate network of interactions involving c-Met residues, Antibodies efficiently down-regulates HGF receptor through a molecular mechanism involving a double proteolytic cleavage, Liver cancer patients had a significantly higher level of serum hepatocyte growth factor than normal controls, As discussed in this review, receptor tyrosine kinase Met and its ligand HGF/SF (hepatocyte growth factor/scatter factor) are essential in the signalling pathways required for embryogenesis and tissue regeneration., Results reveal that a subset of human hepatocellular carcinomas and all liver metastases shared the Met-induced expression signature., Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells., c-Met ectodomain shedding has a role in cancer's malignant potential, c-met-siRNA can down-regulate the expression of c-met and inhibit hepatocellular carcinoma cell proliferation, motility and invasiveness., results suggest that activation of c-Met signaling in prostate cancer cells may lead to induction of spontaneous mutations or genomic instability, which may lead to progression of androgen-independent state, IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells., Processing of the Met receptor results in the release of the cytoplasmic domain and its translocation to the nucleus in cells at low density., Mimp expression reduces hepatocyte growth factor/scatter factor-induced proliferation and scattering by attenuating and altering the downstream signaling of met proto-oncogene., A functional crosstalk between hepatocyte growth factor receptor (MET) and beta-catenin signaling sustains and increases colorectal carcinoma cell invasive properties., genetic association (P = 0.0005) of a common C allele in the promoter region of the MET gene in 204 autism families, Serum-independent growth of 5637 cells involves the transmembrane signaling cascade via EGFR ligand(s) (but not HGF), EGFR, Src and p145(met)., Met activation induces changes consistent with early invasion, such as down-regulation of E-cadherin and anchorage-independent growth of esophageal adenocarcinoma., The alternatively-spliced form of MET may contribute to the development and progression of human cancer., c-Met has a role in progression of esophageal adenocarcinoma, glycosphingolipids, particularly GM2, form a complex with CD82, and this complex interacts with Met and thereby inhibits HGF-induced Met tyrosine kinase activity, as well as integrin to Met cross-talk, Plays a role in the progression of rhabdomyosarcoma., HGF stimulation of c-Met-overexpressing H69 small cell lung cancer cells (40 ng/ml, 15 min) resulted in an increase of reactive oxygen species, Met is necessary for lung cancer cell lines growth and survival., although serine proteases and HGF have quite distinct functions in proteolysis and Met signal transduction, respectively, they share a similar activation mechanism, In lung adenocarcinoma, c-Met activation may take place either ligand-dependently or ligand-independently via c-Met. overexpression., findings show that amplification of MET causes gefitinib resistance in lung cancer by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors, Imbalance in c-Met expression between tumour and surrounding normal tissue is associated with aggressive ductal carcinoma in situ phenotype. c-Met and HGF/SF may contribute to tumour development by different means than those controlled by Her2/neu., c-met is an essential factor in the processes of migration and invasion of hepatocarcinoma cells, The crystal structure of the complex between a large fragment of the human Met ectodomain and the Met-binding domain of InlB., c-MET is associated with FAS and when activated enhances drug-induced apoptosis in pediatric B acute lymphoblastic leukemia with TEL-AML1 translocation, persistent expression of the MET oncogene is mandatory until the advanced phases of cancer progression., These results demonstrate that lysophosphatidic acid regulates c-Met function through PKC delta and E-cadherin., Altered expression of MET and related molecules suggests dysregulation of signaling that may contribute to altered circuit formation and function in autism spectrum disorder, CD44 is an important regulator of HGF/c-Met-mediated in vitro and in vivo barrier enhancement, a process with essential involvement of Tiam1, Rac1, dynamin 2, and cortactin., Fas antagonism by Met is abrogated in human fatty liver disease., The tumor suppressor activity of GPx3 seems to relate to its ability to suppress the expression of c-met., HGF and c-MET are potential orchestrators of invasive growth in head and neck squamous cell carcinoma [review], This study was designed to investigate the roles of HGF/c-Met in tumor progression and metastasis in HepG2 and Hep3B hepatoma cell lines, Co-expression of HGF and c-Met in gastric cancer may promote the progression of gastric cancer., a novel mechanism by which plexin-mediated signaling can be regulated and explains how Sema4D can exert different biological activities through the differential association of its receptor with ErbB-2 and Met., These results demonstrated that VPA inhibited two critical processes of tumor-stromal interaction, induction of fibroblastic HGF production and HGF-induced invasion of HepG2 cells., cooperative role for c-Met and c-Myc in large-cell anaplastic medulloblastoma formation, HGF/c-Met were expressed in serum-starved ARPE-19 cells., MET amplification occurs independently of EGFR(T790M) mutations in lung adenocarcinoma, The expression of c-met was closely related to the invasiveness of cholangiocarcinoma., The expression rate of c-met was higher in adenocarcinomas than adenomas., oncogenic EGFR and c-Met have roles in pathways mediating drug response, p100 MET, corresponding to the entire extracellular region of the MET receptor still spanning the membrane is able to bind HGF/SF and to prevent HGF-dependent signaling downstream of full MET, demonstrating its function as a decoy receptor., Selectivity for specific adaptor protein involvement may be the key that determines the tissue- and cell-type specificity of Met-mediated tumorigenicity in human cancers, Src family kinases activity is important for the growth of colorectal cancer cell lines, although only low activity levels are required, a previously uncharacterized GM2/GM3 heterodimer complexed with CD82 inhibits cell motility through CD82-cMet or integrin-cMet pathway, Report renal expression of alpha-smooth muscle actin and c-Met in children with Henoch-Schonlein purpura nephritis., NK1 variants have no detectable agonistic activity on, behave as bona fide receptor antagonists by blocking cell migration and DNA synthesis in target cells and have strong prospects as therapeutics for human cancer., Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells, MET amplification associated with EGFR amplification is associated with non-small cell lung cancer, c-Met gene amplification is linked to metastatic progression, and is a viable target for a significant subset of advanced CRC., A Met/c-Src-mediated signaling pathway is a mediator of EGFR tyrosine phosphorylation and cell growth in the presence of EGFR tyrosine kinase inhibitors., Usefulness of Frzb in modulating Met signaling as a new treatment strategy for soft tissue sarcomas., the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2) are regulated by MicroRNA miR-199a*, High glucose can induce the expression of c-met, and Radix Astragali can up-regulate the expressions of c-met mRNA and protein in human kidney fibroblasts., analysis of the hepatocyte growth factor-binding site in the immunoglobulin-like region of Met, Amplification of MET is associated with type I endometrial carcinoma tumors, overexpression of c-met is associated with gastric carcinoma, Met-driven invasive growth involves transcriptional regulation of Arhgap12., The relative subcellular distribution of Met may be a valuable biomarker for estimating colon cancer prognosis., identification of HGF/MET mutations in primary lymphedema, lymphedema/lymphangiectasia, and breast cancer-associated secondary lymphedema suggests that the HGF/MET pathway is causal or alters susceptibility for a broad range of lymphedema phenotypes, Disruption of lipid rafts inhibits the activation of PLCr1/PKC and PI3K/PKB signaling pathways by c-Met., CXCR4 and c-Met are widely expressed in rhabdomyosarcoma and, at higher levels, in isolated marrow-infiltrating tumor cells, Phosphorylation of MUC1 by Met modulates interaction with p53 and MMP1 expression.(, the HGF/c-MET axis has a role in guiding stem cells toward brain injury, a novel splice variant of the Met receptor, Cgen-241A, is a potent antagonist of the hepatocyte growth factor/scatter factor-Met pathway, germline c-met missense mutation g.3522G--> A in exon 16 and somatic missense mutation g.3997 T-->C in exon 19 were identified in papillary renal cell carcinoma patients identified, Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression., STAT3 activation and nuclear accumulation in response to Hepatocyte Growth Factor requires nuclear-proximal activated c-Met., HGF and c-Met have roles in growth of aggressive adult T-cell leukemia/lymphoma cells, PTP1B and TCPTP play distinct and non-redundant roles in the regulation of the Met receptor-tyrosine kinase, MET increased gene copy number and primary resistance to gefitnib therapy in non-small-cell lung cancer patients are reported., The abnormal expression of c-met and PCNA protein was related with the oncogenesis of gastric carcinoma., TFE3-renal carcinoma in an adult patient, The epithelial expression of HGFR is elevated in mildly active UC., Steric hindrance of the interaction between HGF beta domain binding to Met is sufficient for inhibiting full-length HGF-dependent Met signaling and cell migration., ability of the leucine-rich repeat fragment to promote Met recycling could account for the increased cell motility induced by this ligand, c-Met kinase activity can up-regulate death receptor expression and thereby sensitize tumor cells to the death receptor ligand TRAIL, our findings provide further evidence that MET may play a role in autism susceptibility., miR-34a has a role in tumor migration and invasion through modulation of the c-Met signaling pathway, a critical role of Met gene dose in non-small cell lung cancer , suggesting that Met may be a specific molecular therapeutic target in selected non-small cell lung cancer patients with increased Met copy number., Perinuclear translocation of c-Met is confirmed in hepatocyte growth factor-stimulated cells; the increase in size of the 50 kDa subunit of c-Met may indicate the involvement of the [alpha]-chain in c-Met intracellular trafficking in chordoma cells., The combination of CD151/c-Met is a novel marker in predicting the prognosis of hepatocellular carcinoma and a potential therapeutic target., This work identifies three miRNAs that negatively regulate MET expression. Inhibition of these endogenous miRNAs, by use of antagomiRs, resulted in increased expression of MET protein., Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain is associated with primary resected lung cancers., MET receptor tyrosine kinase is a therapeutic anticancer target [review], Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes beta-catenin transcriptional activity to drive thyrocyte neoplastic transformation., Distinct recruitment of Eps15 via Its coiled-coil domain is required for efficient down-regulation of the met receptor tyrosine kinase., MET amplification is present in untreated NSCLC and EGFR mutation or MET amplification activates MET protein in NSCLC, NmU may be involved in the HGF-c-Met paracrine loop regulating cell migration, invasiveness and dissemination of pancreatic ductal adenocarcinoma., c-Met plays an important role in bladder cancer development, Lack of oncogenic mutations in the c-Met catalytic tyrosine kinase domain in acral lentiginous melanoma, study determined PAX5 could regulate transcription of c-Met; the phospho-c-Met (active form) & PAX5 were both localized to the same intra-nuclear compartment in hepatocyte growth factor treated small-cell lung cancer cells and interacted with each other, MET as a target of YB-1 that work in concert to promote Basal-like breast cancers (BLBC) growth., Expression of c-Met can be inhibited by RNA interference in flioma cells, which can inhibit the growth and metastasis of glioma cells and induce cell apoptosis., molecular mechanism of activation and the functional role of cancer mutations in altering protein kinase structure, dynamics, and stability., PTEN loss amplifies c-Met-induced glioblastoma malignancy., C-met has a role in endometrial receptivity through its interaction with Plexin B1., These results suggest that disrupted MET signaling may contribute to increased risk for autism spectrum disorder that includes familial gastrointestinal dysfunction., MET increased gene copy number is an independent negative prognostic factor in surgically resected non-small-cell lung cancer, Met is processed in epithelial cells by presenilin-dependent regulated intramembrane proteolysis (PS-RIP) independently of ligand stimulation., c-MET expression was observed in most spinal chordomas and correlated with the expression of CAM5.2, suggesting a relationship to an epithelial phenotype., the relatively infrequent expression of HGF and Met in Wilms' tumor tumorigenesis reflects their roles in nephrogenesis, particularly the mesenchymal-to-epithelial transition, rather than a dependence on oncogenic signaling pathways., SMYD3 has a role in regulation of c-Met expression and in cell migration and invasion induced by HGF, The constitutive activation of nuclear Met-signaling pathway in MDA-MB231 cells, possibly determined at genetic or epigenetic levels of WWOX gene, might participate in breast carcinoma progression influencing invasive/metastatic phenotype., HGF-induced activation of the Met receptor results in TF expression by MB cells and that this event probably contribute to tumor proliferation by enabling the formation of a provisional fibrin matrix., data further support our hypothesis that genetic susceptibility impacting multiple components of the MET signaling pathway contributes to autism spectrum disorder risk, Combination of MET and EGFR inhibitors triggered stronger inhibition on cell proliferation and invasion of MPM cells than that of each in vitro., EGFR T790M mutation and c-MET amplification can occur in tyrosine kinase inhibitor-resistant non-small cell lung cancer with wild-type EGFR. These genetic defects might be related to different survival outcome., HBx induces the expression of c-met through the activation of AP-2 and SP-1 activity at the promoter region in HepG2 cells., CD44v6 is required for InlB-induced c-Met activation in Listeria invasion., Decorin suppresses intracellular levels of beta-catenin, a known downstream Met effector, and inhibits Met-mediated cell migration and growth, An inverse relationship was found between generation of cytoplasmic fragment of MET protein and phosphorylation of MET protein, with a direct involvement of phosphorylated Tyrosine 1001 in protecting MET against its caspase cleavage., Results show that blocking the HGF/c-Met pathway may be clinically useful for the treatment of HNSCC., MET protein is found to be highly expressed in alveolar soft part sarcoma patients, most commonly in the lower extremity (thigh, lower leg, and foot)., Data show that c-Met is the substrate of ST6Gal-I, and that the hyposialylation of c-Met can abolish cell motility in ST6Gal-I-KD HCT116 cells., Results show that overexpression of miR-23b leads to uPA and c-met downregulation and to decreased migration and proliferation abilities of HCC cells., Our data implicate the involvement of cMET in the pathogenesis of myopia in general, as well as more rapid progression in refractive error regardless of the initial refractory ability., The downstream signaling in tumor cells overexpressing Met is not stably suppressed by Met tyrosine kinase inhibitors, even though Met remains fully inhibited., Results demonstrated the presence of c-Met in osteogenic and chondrogenic tissues of developing human mandibles, which indicates possible functions for this receptor during mandibular development., link between the PAR(2) and Met receptor tyrosine kinase signaling in promoting hepatocellular carcinoma (HCC) cell invasion., the MET C allele influences at least two of the three domains of the autism triad, Urinary met may provide a noninvasive biomarker indicative of metastatic prostate cancer and may be a central regulator of multiple pathways involved in prostate cancer progression., MACC1 acts via a specific consensus sequence of the Met promoter, described as an Sp1 binding site., MET may play a critical role in the development of the most aggressive breast cancers and may be a rational therapeutic target., Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer., Critical role for HGF/Met signalling in promoting PGE(2) biogenesis in colorectal cancer cells., observed association between MET Y1253D-activating point mutation and decreased distant metastasis-free survival in advanced HNSCC suggests that MET may be a potential target for specific treatment interventions, a model for a neoplastic pathway where expression of PAX6 from development activates the MET receptor, Infection with H. pylori provokes shedding of the ectodomains of c-Met and E-cadherin. ADAM10 contributes to the shedding of c-Met and E-cadherin., This study is the third independent study to find the rs1858830 C variant in the MET gene promoter to be associated with autism., Report negative action of hepatocyte growth factor/c-Met system on angiotensin II signaling via ligand-dependent epithelial growth factor receptor degradation mechanism in vascular smooth muscle cells., EGFR, c-Met, and VEGFR1 involved in carcinogenesis are well-represented and coexpressed in anal cancers, especially in HIV-positive population, The MET in lung cancer tissues contained nonsynonymous mutations in the semaphorin and juxtamembrane domains but not in the tyrosine kinase domain. East Asians, African-Americans, and Caucasians had different MET genotypes and haplotypes., Exploring the roles of c-met in modulating the motility of cell, by silencing c-met expression in a human hepatoma cell line., Data suggest that the coreceptor function of CD44v6 for c-Met and VEGFR-2 is a promising target to block angiogenesis in pathologic conditions., Accordingly, the present study suggests that MET activation caused by factors other than MET gene amplification is not a suitable surrogate marker of resistance to EGFR-TKIs., Using lung adenocarcinoma samples and cell lines derived from lung adenocarcinomas, we demonstrated that the gene copy number for MET in lung adenocarcinoma tissue samples was increased over EGFR, HGF, and PXN and that it correlated with better prognosis, Results support a role for c-Met as an inhibitor of apoptosis and an activator of Bcl-xl., Histopathology and expression of Met in cancer and its association with clinicopathological characteristics., Liposomal quercetin could suppress the proliferation of culture Eca109/9706 cells by suppressing expression of c-met and VEGF., we aimed to examine the significance of Src-mediated Gab1 phosphorylation in the hepatocyte growth factor (HGF) signaling, the signaling-competent InlB-Met complex assembles with 2, Results show that SGX523 is the most selective inhibitor of MET catalytic activity described to date and is thus a useful tool to investigate the role of MET kinase in cancer without the confounding effects of promiscuous protein kinase inhibition., Data show that Plex-B1 assumes a predictive value for unfavourable outcome when co-expressed with Met., The purpose of this study was to determine if genetic variants in the hepatocyte growth factor receptor (MET) gene are associated with refractive error and ocular biometric measures in a Caucasian cohort., Results provide evidence that autocrine overactivation of the Met- HGF loop enhances systemic metastases in NSCLC., G-CSF-mediated hematopoietic stem/progenitor cells (HSPC) mobilization occurs in part through the HGF/c-Met axis in HSPC and myeloid cells, eliciting increased production of matrix-degrading enzymes and subsequently facilitating egress of HSPC., Stromal changes associated with breast cancer can control proto-oncogene function., Uveal melanomas express HGF, c-Met, EGFR, and IGF-1R, The MET promotes the melanoma cancer phenotype by promoting migration, invasion, resistance to apoptosis, and tumor cell growth., Data show that PF-2341066 reduced HGF-stimulated phosphorylation of c-Met in the tyrosine kinase domain as well as phosphorylation of the downstream signaling effectors, Akt and Erks., evidence suggesting an intriguing relationship between cancer-related genes and schizophrenia susceptibility., Activation of VEGF165-NRP1-c-MET signaling could confer prostate cancer (PCa) cells survival advantages by up-regulating Mcl-1, contributing to PCa progression., High MET gene copy number is associated with non-small cell lung cancer., Inhibition of c-Met blocked the acquired anoikis resistance and restored chemosensitivity in three-dimensional not in two-dimensional ovarian cancer cell cultures, MET activation by its ligand, HGF, also induces drug resistance, Phosphorylation of MET and MET amplification is associated with lung adenocarcinoma., EGFR signaling can regulate MET levels through HIF-1alpha and that MET is a key downstream mediator of EGFR-induced invasiveness in EGFR-dependent NSCLC cells., The MET receptor plays a very important role in facilitating metastasis of RMS cells, blocking of HGF-MET axis might be considered as a therapeutic option for RMS patients, at more advanced and metastatic stages., Plexin B1 may function as a tumor promoter in melanomas not driven by c-Met activation., The cross-talk and balance between HGF/c-Met signal pathways are critical and necessary in the development of new therapies for lung cancer., We now report that monocytes' contact-dependent mitogenicity is controlled by activation-mediated regulation of hepatocyte growth factor, These findings suggest aberrantly down-regulated hsa-miR-34c is a critical factor that contributes to malignancy in human laryngeal carcinoma by a mechanism involving targeting of c-Met., Because enamel organ cells interact with mesenchymal cells directly, and c-Met is expressed in stages at which mesenchymal induction is guided by the dental epithelium, c-Met is related to tooth germ morphogenesis and cell differentiation., HGF and c-Met are widely expressed in pituitary adenomas and may have a role in their angiogenesis and tumorigenesis, An overview of murine Met models in relation to the spectrum of mouse models of breast cancer and a role for the Met receptor in basal breast cancer tumorigenesis, is provided., This immunohistochemical study is the first to document c-Met expression in human embryo minor salivary glands and to suggest the involvement of the c-Met/HGF system in their development, study found four gastric cancer cell lines harbored amplification of c-met locus, and among them, Hs746T had a putative oncogenic mutation with amplification, Our results indicated that the overexpression of c-Met gene played an important role in the progression and development of small cell lung cancer., The current study highlights the significance of HGF/c-Met signaling in the capacity of MSC to restore blood flow after an ischemic injury., c-Met-specific small tyrosine kinase inhibitor SU11274 successfully inhibited primary tumor growth and liver colony formation by human melanoma cells in SCID mice., MET activation as a cause of resistance to c-Src inhibition., These data suggest that polymorphisms in the MET gene may play a role in the susceptibility to develop CRS. Study findings apply to patients with severe CRS unresponsive to surgery., Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer, Data report that Met protein expression and phosphorylation were associated with primary resistance to EGFR TKI therapy in NSCLC patients harboring EGFR mutations, implicating Met as a de novo mechanism of resistance., is overexpressed in chordomas, c-Met antisense oligonucleotides increase the sensitivity of human glioma to paclitaxel., This study did not reveal any prognostic value of c-met or VEGF., Dorsal ruffle microdomains potentiate Met receptor tyrosine kinase signaling and down-regulation, Human hepatocyte growth factor receptor is a cellular coreceptor for adeno-associated virus serotype 3, simultaneous expression of HGF/c-met and three trasducers of tyrosine kinase receptors STAT3, PI3K, RHO in both nodular and extranodular tissues were studied by immunohistochemistry in 50 benign thyroid nodules, 25 associated with Hashimoto's thyroiditis, demethylation of the colon carcinoma cell line HCT116 induces the expression of an illegitimate fusion transcript between an intronic LINE-1 element and the proto-oncogene cMet, Immunohistochemistry in muscle from polymyositis and dermatomyositis patients revealed that HGF was expressed predominantly on infiltrating mononuclear cells and that muscle cells expressed the receptor c-met., The results of this study provided further evidence for a possible role of MET in the pathogenesis of Autism Spectrum Disorders., This study suggested that c-MET overexpression may represent an early chromosome 7 alteration that could play an important role during chordoma pathogenesis., primary myxofibrosarcomas, MET overexpression associated with important prognosticators, and was independently predictive of worse outcomes, in colon cancer sprouty functions as an oncogene and its effects are mediated in part by c-Met upregulation, Results indicate that c-Met/HGF pathway may be a potential target for therapeutic intervention for treatment of EOC., Authors present an analysis of two sequence variants of the MET receptor (hepatocyte growth factor receptor) R970C and T992I (also designated R988C and T1010I)., Results identified Brk and ERK5 as important downstream effectors of Met signaling to cell migration., recurrent glioblastoma multiforme express c-Met at a higher level and that c-Met overexpression is associated with shorter progression-free survival time in patients with glioblastoma multiforme., CD151, c-Met, and integrin alpha3/alpha6 were all overexpressed in pancreatic ductal adenocarcinoma. CD151 and c-Met might be new molecular markers to predict the prognosis of pancreatic ductal adenocarcinoma patients., Allosteric peptide activators of pro-hepatocyte growth factor stimulate Met signaling., c-Met inhibitors PHA-665752 and PF-2341066 have an anti-proliferative role in advanced prostate cancer, MET activating mutations are genetic markers associated with the Cancer of unknown primary origin (CUP) syndrome., study shows decorin blocks several biological activities mediated by Met signaling axis; these effects were mediated by downregulation of noncanonical beta-catenin levels; Myc was downregulated by decorin; phosphorylation of Myc at threonine 58 was induced, Expressed in most neuroendocrine tumors of lung. Coexpression of PAX5 with c-Met or phosphorylated c-Met was present in most of the atypical carcinoids, SCLCs, and large cell neuroendocrine carcinomas., Inhibition of c-Met tyrosine kinase resulted in downregulation of TP53-induced TIGAR and depletion of intracellular NADPH and cell death., Case Report, fibronectin promotes ovarian cancer invasion and metastasis through an alpha(5)beta(1)-integrin/c-Met/FAK/Src-dependent signaling pathway., both binding and orientation is dictated by the c-MET phosphorylated tyrosine and an adjacent arginine forming intra-peptide hydrogen bonds and aligning unidirectionally with complementary charges in the phosphotyrosine binding pocket of c-Cbl., HGF and c-Met may play a role in the progression of endometrial cancer, Our findings establish that oncogene addiction to MET involves Ron transactivation, matriptase as an initiator of c-Met-Akt-mTor-dependent signaling axis in tumors and mTor activation as an essential component of matriptase/c-Met-induced carcinogenesis, Data indicate that MET and LRRK2 cooperate to promote efficient tumor cell growth and survival in these cancers., uncoupled Met down regulation likely functions to amplify the oncogenic signaling of Met in pancreatic tumor cells., There is a positive correlation between the EGFR and c-Met protein expression and the differentiation of non-small cell lung cancer., findings denote hTid-1(S) as an essential regulatory component of MetR signaling, the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors., Report variable expression of MET in different variants of renal cell carcinoma., Tumor MET expression may not predict the risk of venous thromboembolism in cancer patients., EGFR and c-Met may interact in a synergistic manner in the oncogenesis and development of non-small cell lung cancer. Expressions were higher in smokers than in nonsmokers., ARQ 197 safely inhibited intratumoral c-MET signaling., High MET expression and gene amplification is not associated in Western patients with gastric cancer., Increased neuronal Met in amyotrophic lateral sclerosis met-transgenic mice prolongs life span, retards motor neuron and delay disease onset loss., Combined targeting of c-Met and EGFR leads to increased xenograft antitumor activity, These results suggest that the increased MET copy number plays an important role in determining prognosis in gastric cancer patients, in ileal neuroendocrine cancer, HER-2/neu overexpression plays a role in the carcinogenetic process and by triggering the altered expression of c-Met and MTA-1, may activate the molecular pathway(s) promoting tumor progression and metastasis development., Expression analysis of MET, MACC1, and HGF in metastatic colorectal cancer., Discovery of a novel mode of protein kinase inhibition characterized by the mechanism of inhibition of human mesenchymal-epithelial transition factor (c-Met) protein autophosphorylation by ARQ 197., RPTP-beta is a key regulator of Met function., c-Abl interconnecting Met-RTK and p53 core pathways, and its inhibition impairs Met-dependent tumorigenesis. Met ensures cell survival through a new path in which c-Abl and p38-MAPK are employed to elicit p53 phosphorylation and Mdm2 upregulation., The down-regulation of c-Met inhibits proliferation and invasion and increases the chemosensitivity of U266 cells., ovarian carcinomas, the amplification of the MET proto-oncogene is highly selective and commonly occurs in clear-cell adenocarcinoma., chronic lymphocytic leukemic cells express a functional hepatocyte growth factor receptor (c-MET) and hepatocyte growth factor enhanced the viability of these cells through STAT3 phosphorylation, In addition to c-Met, the cross-talk with Axl and/or PDGFR-alpha also contributes to the progression of human bladder cancer, Four biomarkers were identified that appeared to be strongly and consistently modulated by Met inhibition in a panel of Met-addicted gastric carcinoma cell lines., the role of SEPT2 and SEPT11 in the InlB-Met interactions, Decreased antiapoptotic Met signaling in podocytes could contribute to podocyte loss and focal and segmental glomerulosclerosis in Transplant glomerulopathy, important prognostic significance of c-Met for patients with oral squamous cell carcinoma., pMET expression was an independent prognosticator of poor patient outcome, These studies are the first confirm that interference with the HGF/c-met/Stat3 signaling pathway can block tumor cell invasion in an in vivo model., Combined targeting of c-Met and EGFR resulted in an enhanced inhibition of tumor volumes accompanied by a decreased number of proliferating cells and increased apoptosis compared with single agent treatment in vivo., MET amplification is associated with non-small cell lung cancer., Findings show that c-Met enhances the population of glioblastoma stem cells via a mechanism requiring Nanog and potentially other c-Met-responsive reprogramming transcription factors., Oncogenicity of Met mutants results not only from activation but also from their altered endocytic trafficking, indicating that endosomal signalling may be a crucial mechanism regulating receptor tyrosine kinase-dependent tumorigenesis., Data show that miR-198 targets c-MET via its 3'UTR, and that forced expression of miR-198 decreased c-MET expression and diminished HGF-induced phosphorylation of p44/42 MAPK., Overexpression of c-Met oncoprotein is associated with cholangiocarcinoma., c-Met recruits ICAM-1 as a coreceptor to compensate for the loss of CD44 in Cd44 null mice., High level of MET and SOX2 expression were respectively demonstrated in ADCs and SCCs; MET activation was accompanied with exon 19 deletion in ADCs., The observed spectrum of mutations in NVP-BVU972-resistant cells was dominated by substitutions of tyrosine 1230 which plays a key role in inhibitor binding., Secreted OPN, induced by LSF, activates c-Met via a potential interaction between OPN and its cell surface receptor CD44. A significant correlation was observed among LSF, OPN, and activated c-Met levels in HCC., Data show that showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in non-small cell lung cancer (NSCLC) cells through the c-Jun-mediated downregulation of miR-221 and miR-222., MET mutation is associated with treatment response in non-small cell lung cancer., IGF1R overexpression is associated with resistance to cetuximab in metastatic colorectal cancer., MET positive cases according to the Cappuzzo scoring system evidenced both aneuploidy and true amplification., The results demonstrated that both Ezrin and c-Met overexpression were related to the occurrence and progression of gastric carcinoma, Met overexpression, but not met mutation, correlates with progression of non-small cell lung cancer., These data demonstrate that GAB1 is ubiquitinated by CBL and degraded by the proteasome, and plays a role in negative-feedback regulation of HGF/SF-MET signaling., study demonstrated that the HGF/c-Met pathway induces epithelial-mesenchymal transition and inhibition of anoikis in gastric cancer cells. Co-expression of HGF and c-Met has the potential to promote peritoneal dissemination in gastric cancer, These results also show that the extent of advanced cancer traits, such as invasion, may be determined by alterations in individual components of p53/MET regulatory network., Expression of MET in restricted human neocortical regions and its regulation in part by FOXP2 is consistent with genetic evidence for MET contributing to autism spectrum disorder risk., suggest that abnormality of the HGF/MET pathway occurs during the course of progression from non-invasive to invasive pulmonary adenocarcinoma, ability of MET receptors and effectors to be spatially controlled by the endosomal recycling pathway may play a prominent role in cellular functions such as motility, HGF induces vascular smooth muscle cell osteogenic differentiation via c-Met/Akt/Notch3 signalling, highlighting these pathways as potential targets for intervention of vascular calcification., Elevated cancer cell cMET and stromal HGF expression were significantly associated with a worse prognosis, Data suggest that c-Met plays an oncogenic role in the development of NPC and as a potential novel therapeutic target for NPC., the molecular signatures of liver cancer in a c-MET-transgenic mouse model, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer., both primary and lymph-node metastases have relatively consistent EGFR mutations and EGFR mutations are not relevant to changes in c-Met gene copy number., Accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma., c-Met is more likely to be activated in both NRAS-mutated and wt/wt melanomas; melanoma cells with these genotypes, particularly NRAS mutants, are more sensitive to pharmacologic c-Met inhibition, Overall, our findings highlighted the effectiveness of c-MET inhibition in delaying the onset and progression of bone metastases., Met and EGFR to be released from lipid rafts, thus leading to their activation in a ligand-independent manner., qPCR revealed approximately 10% of white patients with gastric cancer harboring MET copy number gain (CNG)of five or more copies., Protein-tyrosine phosphatase 1B modulates early endosome fusion and trafficking of Met and epidermal growth factor receptors., Review, High MET gene dosage was not related to primary tyrosine kinase inhibitor resistance and the incidence was increased after chemotherapy, suggesting high MET gene dosage may also be related to chemotherapy resistance., Met stimulates hepatocyte glucose uptake through crosstalk with insulin receptor., PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype., MET variants may be relevant to autism susceptibility in the Chinese Han population, Immunohistochemical characterization of HGF/C-MET system pathways in benign and malignant histotypes of thyroid nodules., overexpressions of FASN and p-c-Met were observed in a subset of thyroid carcinomas of follicular origin, multiple receptor tyrosine kinases are amplified in a subset of glioblastoma subclones, epidermal growth factor receptor, MET and platelet-derived growth factor receptor alpha, The structure of the MET receptor, the activated pathways, the main genomic anomalies in lung cancer & the development of MET inhibitors are reviewed. Review., these results are the first to identify EGFR and MET-receptor-regulated miRNAs representing oncogenic signaling networks in NSCLCs., The expression of ezrin, HGF and/or c-met might be closely related to the carcinogenesis, progression, clinical biological behaviors and prognosis of gallbladder adenocarcinoma., Concomitant downregulation of miR-1 and increase of MACC1 can thus contribute to MET overexpression and to the metastatic behavior of colon cancer cells., expression of c-Met in tumor cells from patients with classical Hodgkin's lymphoma strongly correlated with a favorable prognosis in two independent cohorts., Data show that c-Met induces FAK and Pyk2 phosphorylation in medulloblastoma cells., inhibition of Met, hypoxia inducible factor 1alpha, vascular endothelial growth factor A, and induction of thrombospondin-1 and TIMP3 by decorin, High c-MET/phospho-MET protein expression and MET gene copy number is associated with nonsquamous non-small cell lung carcinomas., Increased MET copy number and MET overexpression are negative prognostic factors for surgically resected in non-small cell lung cancer, Although c-Met expression was not significantly associated with c-Met gene amplification, it may be a useful predictive marker of recurrence in resected HCC patients., MET gene copy number by silver in situ hybridization and protein expression is not associated with non-small cell lung carcinomas., Data indicate that MET-mediated resistance to lapatinib is a novel mechanism of resistance to HER2-targeted agents in gastric cancer cells., Plasma cell membrane localization of c-MET is associated with malignant mesothelioma., Met-dependent Cbl loss may also promote cross-talk through indirect enhancement of EGF receptor signaling., Expression of c-Met is one of the factors that distinguishes normal from malignant plasma cells and indicates that the HGF/c-Met system is activated in multiple myeloma patients., results demonstrate the involvement of the disialoganglioside G(D2) in MDA-MB-231 cell proliferation via the constitutive activation of c-Met, c-Met, epidermal growth factor receptor, and insulin-like growth factor-1 receptor are important for growth in uveal melanoma and independently contribute to migration and metastatic potential, miR-1 can have a tumor suppressor function in colorectal cancer by downregulating MET oncogene both at RNA and protein level and that reexpression of miR-1 leads to MET-driven reduction of cell proliferation., Met signals through a cortactin-Gab1 scaffold complex, to mediate invadopodia., MET initiates the transformation of a cell population that has features of osteo-progenitors., high levels of cMET and p-cMET were seen in all breast cancer subtypes and correlated with poor prognosis, SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk, The Met signaling pathway did correlate with MetMAb treatment response initially and at the time of recurrence., High phosphorylated-c-Met is associated with early distant organ metastasis in pancreatic ductal adenocarcinoma., In human gastric cancer cell line SGC7901 cells, Lentivirus-mediated RNAi significantly reduced both c-Met mRNA and protein expression, which resulted in suppressing the cell proliferation, invasion and adhesion to peritoneum., context-specific processing of c-Met protein is implicated in HCC progression in stressful microenvironments., To determine if mutation of HGF/MET pathway genes is a mechanism for pathway dysregulation, conducted a mutational analysis of three key components of this pathway, High expression of MACC1 or MET was associated with reduced relapse-free survival and the prognosis was worse when both genes were highly expressed, The HGF/c-Met signaling pathway may be involved in the pathogenesis and progression of colon cancer. C-Met overexpression can be used as a useful parameter to evaluate the prognosis of colon cancer., immunohistochemical analysis of NOTCH1-3, JAGGED1, cMET, and phospho-MAPK in 100 carcinomas of unknown primary, Fas ligand enhances malignant behavior of tumor cells through interaction with Met, hepatocyte growth factor receptor, in lipid rafts., The findings indicate that MET variances and MET/AKT interaction may affect facial emotion perception., Hugl-2 induces MET and suppresses Snail tumorigenesis., a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe., amplification of ERBB4, C-MET and CD44 was significantly associated with certain clinicopathological characteristics, particularly tumor differentiation and cancer-related death and poor survival., MET activation in glioblastoma is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target., Reduced LFNG expression facilitates JAG/NOTCH luminal progenitor signaling and cooperates with MET/CAVEOLIN basal-type signaling to promote basal-like breast cancer., identified an exosome-specific melanoma signature with prognostic and therapeutic potential comprised of TYRP2, VLA-4, HSP70, an HSP90 isoform and the MET oncoprotein, c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas, MET protein overexpression was observed in 104 of 438 cases., report here the results of a genome-wide short hairpin RNA screen for genes that are lethal in combination with p53 activation by Nutlin-3, which showed that the ATM and MET kinases govern cell fate choice upon p53 activation, The results of yhis study suggested that MET gain was also common in diffuse astrocytomas (38%), but less frequent in oligodendrogliomas (16%). MET gain in diffuse astrocytomas was associated with shorter survival., These results show a widespread dependence of acute myeloid leukemia cells on autocrine activation of MET., HGF down-regulated c-Met receptor expression, whereas it up-regulated pro- and active/mature forms of ADAM10 and ADAM17 expression, which resulted in enhanced sMet production, C-Met proto-oncogene enhances the migration and invasion of tongue cancer cells through the expressions of matrix metalloproteinase-1, -2, and -9, and promotes tongue cancer cell growth, A missense mutation (c.3328G > T, p.Val1110Leu) in the c-MET gene was identified in a family with hereditary papillary renal carcinoma., Results show that the cellular receptors, FAK, CD44v6, c-Met and EGFR, are biomarkers of survival and tumour progression in colorectal cancer. Increased staining for each receptor was also followed by expression elevation of at least one other marker., our findings suggest that Met is a functional marker of glioblastoma stem cells and a candidate target for identification and therapy of a subset of glioblastomas., miR-410, a direct regulator of MET, may function as a tumor suppressor in human gliomas., demonstrate that vascular endothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhanced recruitment of the protein tyrosine phosphatase 1B (PTP1B) to a MET/VEGFR2 heterocomplex, MACC1 and c-met have an important function in the differentiation, invasion, and metastasis of NSCLC, Met signaling regulates the secretion of the pro-angiogenic chemokine interleukin-8/CXCL8, Genetically determined decrease in MET protein production may lead to a reduction in immune regulation in mothers who produce autism-associated antibodies to fetal brain proteins., High GCNs of MET and HGF associate with an increased risk of trastuzumab-based therapy failure in HER2-positive MBC., Results suggest the interaction of the Cap domain of InlB from one and the Sema domain of MET from another 1, c-met overexpression in SSC fibroblasts may be a negative feedback against cutaneous fibrosis., an anti-apoptotic role of caspase-cleaved GAB1 in HGF/SF-MET signaling., We show that a common, functional autism spectrum disorder (ASD) risk variant in the Met Receptor Tyrosine Kinase (MET) gene is a potent modulator of key social brain circuitry in children and adolescents with and without ASD., the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the beta-catenin/c-Myc pathway., In small cell lung cancer and neuroendocrine tumors MET mutations are relatively rare; detected mutations were located in the juxtamembrane domain and were of no functional relevance as they did not influence c-Met phosphorylation, Co-expression of c-Met and Integrin alpha5beta1 has mechanical significance in the early stages of human gastric cardia adenocarcinoma., The binding ability of mouse HGF alpha-chain, or of beta-chain, to human c-Met was lower than that of human HGF., Low c-Met is associated with gastric cancer., Results of the current study suggested that DCP and c-Met are commonly and concurrently expressed in hepatocellular carcinoma., c-Met is associated with poor pathologic features and prognosis in renal cell carcinoma, the link between p38 and c-Met is implicated in the progression of human cholangiocarcinoma., These results describe a unique role for EGFR and Met in mammary epithelial cells., Met kinetic signature derived from the response to HGF/SF in a cellular model predicts breast cancer patient survival, Glycosylation is required for c-Met membrane targeting., polymorphisms in our study groups suggests that polymorphisms in the minimal promoters of these genes are not involved in the pathogenesis of ROP., MET receptor tyrosine kinase has been proposed as a candidate risk gene for autism spectrum disorder., MET dimerization by the HGF splice variant NK1 may be ligand-mediated with a NK1 dimer at the center of the 2, The effect of MUC1 and EGF on these phenotypes was dependent upon c-Met activity., LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation., S1PR1 and ITGB4 transactivation are rate-limiting events in the transduction of HGF signals via a dynamic c-Met complex resulting in enhanced EC barrier integrity, Patients with localised renal-cell carcinoma and the MET polymorphism rs11762213 might have an increased risk of recurrence after nephrectomy., Aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future., Silencing of miR-34a and upregulation of c-Met, Snail, and beta-catenin expression is associated with liver metastases of colon cancer., High MET signaling is associated with glioblastoma., Neuropilin-1/c-met signalling pathway mediates rhodocetin-alpha,beta restructuring of matrix contacts in endothelial cells., Studies indicate that NK4 hepatocyte growth factor fragement inhibits hepatocyte growth factor (HGF)-mediated hepatocyte growth factor receptor MET tyrosine phosphorylation by competing with HGF for binding to MET., findings show that miR-34b may play an important role in non-small cell lung cancer progression; miR-34b downregulates Met, with subsequent changes of downstream p53 and Mdm2, and inversely p53 upregulates miR-34b in a feedback loop, NK4 has anti-proliferative and anti-invasive effects in cholanciocarcinoma mediated the HGF/Met pathway., HGF enhances migration of chondrosarcoma cells by increasing matrix metalloproteinase-2 expression through the c-Met receptor/PI3K/Akt/PKCdelta/NF-kappaB signal transduction pathway.., c-Met oncogene overexpression is an important parameter in cervical early oncogenesis and may have a role in malignant transformation of cervical epithelial cells., Data indicate that the median MET copy number in 266 cases of gastric cancer was 1.7, with a range of 0.41 to 21.3., MET and ALK may have roles in poor survival in Ewing sarcoma, KRC-408 is a novel therapeutic candidate effective against gastric cancers that overexpress c-Met, inhibiting cell proliferation and angiogenesis., MET and associated genes showed a clear deregulation in vestibular schwannomas., Suppression of STAT3 phosphorylation with WP1193 reduced HGF expression in DeltaEGFR-expressing GBM cells., Silencing of SNX2 markedly alters sensitivity to anticancer drugs targeted to c-Met., Report MET copy number gain as a poor prognostic factor in primary intestinal diffuse large B-cell lymphoma., Radiation Upregulates c-Met Expression and Signaling Activity in Human Breast Cancer Cell Lines., We found that HGF coexpression is a key predictor of response to c-MET inhibition among the examined factors and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET inhibition in responsive and nonresponsive cells, Soluble serum c-Met expression correlates with the tumor c-Met expression level and tumor size in humans; high soluble c-Met predicts poorer outcome., MET expression is higher in advanced versus no/limited multiple myeloma lytic bone disease. All bone marrow biopsies show MET expression., Results document MET mutations in anaplastic lymphoma kinase-rearranged (ALK+) lung adenocarcinomas. The pathogenic role of these MET mutations is not entirely clear., MYO5B is epigenetically silenced in gastric cancer cells by DNA methylation and histone modification. Inactivation of MYO5B in gastric cancer cells expressing MYO5B inhibits HGF-stimulated MET degradation with sustained c-MET levels and signaling., HGF/c-Met pathway signaling may influence OVCA chemosensitivity., MET is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with poor prognosis., Data indicate that EGFR T790M as the most common mechanism of acquired resistance, whereas MET amplification, HER2 amplification, and small cell histologic transformation occur less frequently., The majority of penile squamous cell carcinomas exhibit c-MET expression which is not associated with oncogene amplification, but might be attributable to polysomy-7., Although the overall percentage of patients exhibiting c-MET amplifications (6.1% [4/66]) did not change with Neoadj-Chemo, two patients transitioned from negative to positive c-MET amplification, and two patients reversed these changes post-Neoadj-Chemo, IGF-1-induced delayed MET activation occurs in cell lines which express both receptors, suggesting that IGF-1R-mediated MET activation may contribute to tumorigenic properties of multiple cancer types when both growth factor receptors are expressed., HGF and Met may exert functions in the development of Synchronous liver metastasis when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, High expression of c-Met is closely related to tumor metastasis in colorectal carcinoma patients., MET and EGFR are overexpressed in esophageal carcinosarcoma suggesting molecular targeted therapies might be an effective line of treatment., our findings indicate the therapeutic potential of targeting both c-Met and VEGFRs simultaneously with a single small-molecule inhibitor for the treatment of human cancers, Suggest that MET and MST1R are independent prognostic factors in classical classical Hodgkin's lymphoma, and may allow the identification of a subgroup of cHL patients who require more intensive therapy., Cross-talk between FPR2 and HGF receptor in human prostate epithelial cells., Data indicate that miR-101 directly targets c-Met via its 3'-UTR., The data reveal the novel function of c-Met in the process of brain metastasis and its potential as a preventive and/or therapeutic target in this disease, AXL and MET crosstalk to promote gonadotropin releasing hormone (GnRH) neuronal cell migration and survival., miR-27a regulates MET, EGFR, and Sprouty2 in lung cancer., Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene., Met-induced blebbing has an important role in cell detachment, amoeboid motility and invasion ability, which are utilized by cancer cells for migration and metastasis, These findings suggest that SB365 docks at an allosteric site on c-Met and thereby targets c-Met signaling pathway, cell growth/angiogenesis inhibition and apoptosis induction., the reduced expression of phosphor-EGFR and c-MET is chiefly responsible for all events of blocking metastasis, Review discusses issues related to identification of tumorigenic clones driven by MET in the context of genetically heterogeneous tumors and strategies aimed at eradicating cancer stem cells., Data show that the expression of miR-449a was reciprocally correlated with c-Met in non-small cell lung cancer (NSCLC) tissues., c-Met immunohistochemical expression is an independent predictor of outcomes in patients with glioblastoma multiforme treated by standard of care., The MET(-) RON(-) phenotype retained its prognostic impact after subgroup analysis., the proteolytic activity of ADAM10/17 is essential for regulating HGF/c-Met signalling during acute liver damage and following regeneration., The mechanism of increased invasiveness upon EGFR and p53(R175H) expression may be the result of increased c-Met activation., The expression of ST3GAL4 leads to SLe(x) antigen expression in gastric cancer cells which in turn induces an increased invasive phenotype through the activation of c-Met, data suggest that the c-Met-N375S sequence variant may not play a significant role in cancer susceptibility and the prognosis of lung cancer patients, evaluated the survival impact of MET expression in patients with BRAF(V600E/K) advanced melanoma treated with vemurafenib, MET overexpression is an independent prognostic factor in gastric carcinomas, Studied the expression of MACC-1 and c-MET in gastric cancer, and correlated this expression with clinicohistological parameters and patient prognosis., The pro-metastatic gene c-Met as a potential miR-409-3p target., findings show that a significant percentage of breast tumors coexpress MET and ERBB2; ERBB2(+) breast cancers with MET(+)/ERBB2(+) subpopulations may have an innate resistance to ERBB2 inhibition, Amplication of the MET protooncogene has been associated with resistance to gefitinib or erlotinib in about 5% of patients, initially responsive to the drug. Somatic mutations in the TK domain of MET have been described in non-small cell lung cancer, Network models inferred from the data revealed a conserved set of signaling pathways and RTK-specific features that grouped the RTKs into three distinct classes, Given these findings, the c-Met pathway is a logical therapeutic target in RCC, and several agents are in clinical testing with early signs of efficacy., MET activation can mediate resistance even to dual anti- ERbB therapies, suggesting a focus for possible deliberate molecular design of multi-targeted therapeutics- in this case, targeting both MET and ERBb pathways, The results indicated that long-term androgen deprivation resulted in a signaling pathway switch from AR to c-Met in androgen-sensitive cells, which was confirmed by immunofluorescence imaging and western blot analysis, Data indicate that binding between hepatocyte growth factor (HGF)-alhpa and tyrosine kinase MET was disrupted by onartuzumab., increased tumor c-MET and HGF expressions were associated with favorable disease attributes but not with survival., evaluated mutations in four driver genes, epidermal growth factor receptor (EGFR), Kirsten ras oncogene (KRAS), c-MET, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), in Chinese lung adenocarcinoma patients, a significant inverse correlation between miR-34c expression levels and MET immunostaining was found in prostate cancer patients. These findings provide a novel molecular mechanism of MET regulation in prostate cancer., discuss the SOCS1-dependent regulation of MET signaling as an important mechanism underlying the tumor suppressor role of SOCS1 that is relevant not only to hepatocellular carcinoma but also to other types of cancers., Knockdown of 6PGD significantly inhibited phosphorylation of c-Met at tyrosine residues known to be critical for activity. This downregulation of c-Met phosphorylation correlated with inhibition of cell migration in vitro., This review describes the critical role of the HGF/c-Met pathway in cancer, as well as the preclinical and clinical investigations on c-Met inhibitors in solid tumors, with emphasis on small-molecule inhibitors in gastrointestinal cancers. [review], Decorin may interfere with angiogenesis by downregulating hypoxia-induced Met, Rac1, HIF-1alpha and VEGF expression in RPE cells, which suggests a potential strategy for the inhibition of CNV., activation through phosphorylation is assosiated with micropapillary pattern and small cluster invasion in lung adenocarcinoma, These findings reveal a novel, specific inhibitory function of LECT2 in hepatocellular carcinoma by the direct binding and inactivation of MET., our findings indicate that EGFR inhibition in GBM induces MET activation in GSCs, which is a functional requisite for GSCs activity and thus represents a promising therapeutic target., Our results strongly suggest that paracrine HGF-induced activation of MET-mediated signaling pathways plays an important role in the pathogenesis of peritoneal carcinomatosis in scirrhous gastric cancer., These results suggest that overexpression of TGF-a through induction of EGFR-MET interaction contributes to cetuximab resistance in colorectal cancer cells., Met can directly inhibit caspase-3 by way of a novel mechanism and promote hepatocyte survival. The results presented here will further our understanding of the mechanisms, High expression of both MACC1 and MET may relate to distant metastasis in colorectal cancer., the Met-dependence receptor in addition to its well-known role in survival signaling mediated by its kinase activity, also participates in the intrinsic apoptosis pathway through the generation of p40 Met., C-Met is independently associated with basal-like subtype of breast cancer., Gefitinib inhibits invasive phenotype and epithelial-mesenchymal transition in drug-resistant NSCLC cells with MET amplification, c-MET inhibitors (tivantinib and crizotinib) suppress the growth of aggressive thyroid cancer cells, and this potential therapeutic benefit results from their non-MET-targeting effects., Data indicate that coexistence of EML4-ALK fusion or ALK copy number increase and EGFR, MET, and KRAS mutations in tumor tissue from two treatment-naive Chinese non-small cell lung cancer (NSCLC) patients., MET gene copy number gain is associated with stage I lung adenocarcinomas., c-MET overexpression is associated with hepatocellular carcinoma., Studies indicate a significantly poorer overall survival in patients with high c-Met expression., Subjects with both MET rs1858830 CC genotype and high air pollutant exposures were at increased risk of autism spectrum disorder compared with subjects who had both the CG/GG genotypes and lower air pollutant exposures., Studies suggest that although serum proto-oncogene proteins c-met (MET) and hepatocyte growth factor (HGF) may serve as predictive biomarkers for MET therapeutics, data do not support their use as pharmacodynamic biomarkers for onartuzumab., miR-26a could suppress tumor angiogenesis of hepatocellular carcinoma (HCC) through HGF-cMet signaling., MET dependent epithelial-to-mesenchymal transition plays an important role in the adverse clinical behavior of small cell lung cancers., LKB1 expression in cancer cell resulted in dephosphorylation of several tumor-enhancing RTKs, including ErbB2, hepatocyte growth factor receptor (c-Met), EphA2, rearranged during transfection (RET), and insulin-like growth factor I receptor., This review showed that MET receptor tyrosine kinase as an autism genetic risk factor., c-Met activation may have a strong influence on keloid pathogenesis. [, We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance in patients with gastric adenocarcinoma, c-Met and CD44v6 receptors have roles in autocrine TGF-beta1 signaling in interstitial lung disease, CK5/6, but not c-Met expression, seems to be important in lymphatic metastasis, Collectively, these findings suggest that the combinatorial inhibition of MET and Top1 is a potentially efficacious treatment strategy for Small cell lung cancer ., High levels of c-Met receptor mRNA in gastric tumor samples are associated with greater depth of invasion, increase in lymphatic metastasis, high frequency of poorly differentiated or undifferentiated tumors, & increase in the gastric cancer staging., results suggest that the dual blockade of mutant EGFR and Met by crizotinib and a new generation EGFR-TKI may be promising for overcoming resistance to reversible EGFR-TKIs but careful assessment is warranted clinically., These data suggest that tumors displaying MET aberrations achieve plateau responses by MET monotherapy and do not receive further benefit by addition of cytotoxic treatments., Increased MET gene copy number is associated with response to chemotherapy in lung adenocarcinoma., The expression of c-Met mRNA was also significantly downregulated., The positivity rates for c-MET and phosphorylated-MET were higher in gastric adenocarcinoma than in adjacent tissue, and they were associated with lymphatic metastasis and prognosis., higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis, Inhibition-related MET accumulation is associated with reduced Tyr1003 phosphorylation and MET physical association with the CBL ubiquitin ligase with concomitant decrease in MET ubiquitination., Studies indicate that proto-oncogene proteins c-met (Met) signals post-internalisation from endosomal compartments., In Alzheimer's disease brains, a marked decline in MET was found in hippocampal pyramidal neurons compared to controls., Colon cancer initiating cells rely on MET signaling for resisitance to EGF receptor inhibitors., This study shows a low frequency of MET mutations and amplification in this cohort of oropharyngeal squamous cell carcinoma., RANK- and c-Met-mediated signal network promotes prostate cancer metastasis or colonization to bone., c-MET expression in patients with spinal chordoma was found to be correlated with a younger patient age and a favorable prognosis., Positivity for HER2, MET and FGFR2 alternations was found in 23 (13.4%), 21 (12.2%) and 9 (5.2%) patients., Upregulation of MET is associated with subclinical central lymph node metastasis in papillary thyroid microcarcinoma, CMet plays no relevant role in most oesophageal squamous cell carcinomas but its overexpression seems to be a key oncogene in about 35% of oesophageal adenocarcinomas, representing a highly promising therapeutic target and prognostic factor., Migration of MSC to apoptotic cardiac myocytes and fibroblasts was driven by hepatocyte growth factor (HGF), and platelet activation was followed by HMGB1/TLR-4-dependent down-regulation of HGF receptor MET on MSC, High MET expression is associated with breast cancer., findings indicated that miR-199a-3p target HGF/c-Met signaling pathway which is crucial for renal cell carcinoma (RCC) development and suggest that miR-199a-3p may serve as a potential target miRNA for RCC therapy, Findings suggest that MET may be a therapeutic target in TNBC and that the combined therapy targeting MET and EGFR may be beneficial for the treatment of triple-negative/basal-like breast cancer (TNBC/BLBC)patients., miR-608 and miR-34a regulate chordoma malignancy by regulating EGFR, MET and Bcl-xL, Overexpression of MET is associated with gastric adenocarcinoma., Data shows that MET and RON are regulated by PAX8 in non-small cell lung cancer., these data provide evidence in support of a significant role for HGF-induced c-Met/PI3k/Akt signaling and NADPH oxidase activation in lamellipodia formation and motility of lung endothelial cells., The present report expands the role of MET activation as a potential target across all pRCC subtypes. These data support investigating MET inhibitors in pRCC in correlation with MET activation status., MET immunohistochemistry remains the most robust predictor of OS and progression-free survival benefit from O+E relative to all examined exploratory markers., these results identify Grb2 and Shc as central signaling effectors of Met-driven progression of intestinal epithelial-derived cancers. Notably, they suggest that Grb2 may represent a promising target for the design of novel colorectal cancer therapies., Receptor-targeted therapeutics for both MET and FN14 are in clinical development, the use of which may mitigate the metastatic potential of NSCLC., MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer., Our study demonstrated for the first time that MET receptor expression, but not MET gene amplification, is significantly increased in ALK(+) NSCLC, results suggested that genetic variants in ACAN and MET are associated with HM. Functional roles of ACAN and MET in the development of HM need to be further investigated, These data suggest that inhibition of Pim regulates both the phosphorylation of eIF4B and the levels of MET protein in vivo., Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer., Results indicate that c-Met induces distinct cell morphology alterations depending on the stimulus that activates c-Met., Our data indicated that the combination of IR with a MET inhibitor, such as PHA-665752, might be a promising therapeutic strategy for NPC., In patients with recurrent/metastatic gastric cancer, MET amplification and strong protein expression are not rare and appear to be significantly associated with unfavorable clinical outcomes., Overexpression of MET is associated with papillary thyroid carcinomas., c-Met expression and c-Met gene amplification were not associated with survival outcomes in tonsillar squamous cell carcinoma patients., MET expression is a prognostic factor for disease-specific survival in breast cancer patients receiving neoadjuvant chemotherapy., Significant correlation between MET and TNS4 expression in human colon carcinoma and ovarian carcinoma suggests TNS4 plays a critical role in MET stability in cancer., Activation of c-Met and upregulation of CD44 expression are associated with the metastatic phenotype in the colorectal cancer liver metastasis model., These results indicated that c-MET overexpression might play an important role in acquired resistance to cytotoxic anticancer drugs, USP8 is involved in deubiquitination of LRIG1, influencing the efficiency of Met degradation., Met needs to traffic to a perinuclear endosome to trigger optimal membrane ruffling, cell migration and invasion., miR-34a could inhibit Akt [PKB (protein kinase B)] phosphorylation, which was restored by the overexpression of both PDGFR and MET., Data show that MET is not overexpressed in urothelial cancer but rather downregulated in a fraction of cancers., high expression of c-MET in primary tumors increased the risk for tumor recurrence after hepatic metastasectomy in patients with colorectal cancer, selected 68 different antibodies that compete with HGF for binding to MET. HGF-competing antibodies recognized 4 distinct hotspots localized in different MET domains, ErbB3, ErbB4, and MET showed marked expression in 76%, 98%, and 96% of ovarian carcinoma cases., Computation biology data showed that EGFR and MET drive the cancer pathways in glioblastoma individuals., MET up regulation suggesting role for the MET signaling pathway in the development of these tumors., Results indicate that oridonin exerted anti-tumor growth on gastric cancer SNU-5 in vitro and in vivo by direct regulation of c-Met signaling pathway., Increased MET gene copy number or protein expression was significantly associated with poorer survival in patients with surgically resected non-small cell lung cancer., In CLI patients a significant decrease in serum HGF levels, concomitant with a loss of skin HIF-1alpha stabilization and a lack of c-Met phosphorylation were seen, probably driving a decrease in wound-healing functions., Data indicate that both hepatocyte growth factor (HGF) and hepatocyte growth factor receptor c-Met are increased after NACT (Neo Adjuvant Chemotherapy)., MET, HER3, IGF1R, and INSR pathways activation represent novel mechanism underlying lapatinib unresponsiveness in HER2+ gastric cancer. Combination strategy may be recommended in treating patients with HER2+ gastric cancer with these pathways activation, Compared to IHC, SRM provided a quantitative and linear measurement of Met expression, reliably distinguishing between non-amplified and amplified MET tumors., findings display a novel molecular mechanism of c-Met regulation in HCC and strategies to increase miR-181a5p level might be an alternative approach for the enhancement of the inhibitory effects of c-Met inhibitors, MET amplification and mutation is associated with metastatic burden and high-grade histology in breast cancer., results provide evidence for a functional role of MET/PAK1 signalling in pancreatic adenocarcinoma, cMET has been implicated in the development and/or progression of triple-negative/basal breast cancer and is overexpressed in at least some triple-negative breast cancers, Results show that MET genetic abnormalities occur in diverse genitourinary malignancies and are associated with a worse prognosis in a phase I setting., The presented data subclassified colorectal cancers (CRCs) based on their activated signaling pathways and identify a role for c-MET and IGF1R-driven PI3K signaling in CRCs, which is superior to KRAS mutational tests alone., Our findings reveal for the first time an essential role of nuclear MET association with SOX9/beta-catenin in castration-resistant prostate cancer in vitro and in vivo, Results show that GD3S regulates stem cell function via c-Met and the expression of GD3S is regulated by FOXC2, a transcription factor functioning downstream of several epithelial-mesenchymal transition signaling pathways., Data indicate that the fusion arose from translocation events involving introns 3 or 8 of protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1) and intron 1 of hepatocyte growth factor receptor MET., reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC., It is prominently expressed at the site of bone metastasis in renal cell carcinoma., HIF-1 and HIF-2 directly activate the expression of AXL and GAS6/AXL signaling uses lateral activation of the met proto-oncogene (MET) through SRC proto-oncogene nonreceptor tyrosine kinase to maximize cellular invasion., Case Report, Data indicste that the expressed single-chain variable fragment (scFv) antibody could bind to hepatocyte growth factor receptor (HGFR) specifically., Results show MET rs40239 may serve as a prognostic biomarker in locoregional gastric cancer and suggest that genetic variants of c-MET may show sex-related differences in the impact on clinical outcome., Metastatic lesions have higher expression of c-MET expression than primary tumors., An autocrine HGF/cMET loop sustains multiple myeloma angiogenesis and represents an appealing new target to potentiate the antiangiogenic management of patients with multiple myeloma., This study is the first suggestion of a potential association between c-Met activation and formation of tumor budding/sprouting at the invasive front., Tivantinib activity is independent of MET signaling in NSCLC, Report poor prognosis/survival in luminal breast cancer patients with circulating tumor cells co-expressing MET and CD47., This study provides an assessment of tumor cMET gene copy number changes and protein overexpression incidence in a cohort of Chinese GC patients., Invasion in LAD cells via inactivation of Akt signaling by targeting c-Met., Three decades after its discovery the MET oncogene, expressed in normal and cancer stem cells, appears to be a key player in cancer onset and progression. The oncogenic role is sustained both by wild-type MET and by a genetically altered, constitutively activated form. [Review], These findings suggest that TNF-alpha fosters a HGF/MET pro-invasive paracrine loop in tumors., Therefore, these results suggest that SB365 is good candidate as a natural product for use in the treatment of Met-amplified non-small cell lung cancers, MET mutation is associated with neoplasms., c-Met upregulated FZD8 through the ERK/c-Fos cascade in HN-CSC. Taken together, our results offer a preclinical proof-of-concept for targeting the c-Met/FZD8 signaling axis as a CSC-directed therapy to improve HNSCC treatment, There were statistically significant correlations between the expression of PDGFR-alpha, c-Met, and EGFR and disease-free survival, MET amplification was detected in 2.6% of patients with solid tumors and was associated with adenocarcinomas, high-grade histology, and higher metastatic burden., Urinary soluble Met levels distinguish patients with bladder cancer from those without., The study reports that two histidine residues separated by a 10-amino-acid spacer (H1068-H1079) located in the juxtamembrane region of c-Met function as a putative novel nuclear localization signal., this study suggests that MET mRNA expression assessed by RNA ISH could be useful as a potential marker to identify MET oncogene-addicted GC., Findings establish the importance of MET in prostate cancer progression but show tumors heterogeneity with Met copy-number gain and expression when met gene is amplified., Her2/Her3 and Met/Her3 were verified in human GC., We conclude that the decreased expression of the tumor-suppressive miR-23b/27b cluster enhanced cancer cell proliferation, migration and invasion in BC through direct regulation of EGFR and c-Met signaling pathways, Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer Chinese patients., MCM7 is essential for RNA splicing of epidermal growth factor receptor, c-Met, and platelet-derived growth factor receptor, c-Met targeting enhances the effect of irradiation and chemical agents against malignant colon cells harboring a KRAS mutation., EGFR-mutated patients tended to be female and non-smoker and experienced a prolonged OS suggesting a possible positive prognostic effect. c-MET mutations did not affect survival. Target therapy might be considered in EGFR and c-MET-mutated patien, Case Report, a novel alternatively spliced inhibitory isoform of Met stimulates muscle cell differentiation, which confers a new means to control muscle differentiation and/or regeneration, Data indicate that ascites-mediated phosphorylation of proto-oncogene protein c-met (c-Met) is inhibited by c-Met inhibitor PF04217903., The aim was to quantify the level of serum MET DNA, analyze its diagnostic value, and provide a novel biomarker for lung cancer., Two thirds (67%) of lung cancers do not have gains in MET gene copy numbers, whereas 3% show a clear-cut high-level amplification, Taken together, these results demonstrate that miR-335 suppresses breast cancer cell migration by negatively regulating the HGF/c-Met pathway., MET may indicate the presence of cancer stem cells facilitating radioresistance as shown by increased ALDH expression, HGF mediated resistance to alectinib, but not to crizotinib, via the MET signal, that alectinib activated the MET signal in ALK-positive non-small cell lung cancer., expression of HGFalpha or cMet was closely correlated with VEGFC, lymphatic microvessel density and metastases of lymph nodes, indicating HGFalpha, cMet and VEGFC may perform important and collaborative actions in lymphangiogenesis and lymphatic metastasis of primary non-small-cell lung cancer, Tumor-suppressive miR206 inhibited dual signaling networks activated by MET and EGFR in lung squamous cell carcinoma., discover a pathway where ETS1 advances melanoma through the expression of MET via PAX-dependent and -independent mechanisms, residual MET kinase activity can be preserved in the presence of a wide range of concentrations of the competitive MET tyrosine kinase inhibitor crizotinib, Meg3 overexpression in insulinoma cells down-regulated the expression of the protooncogene c-met., Rilotumumab had an exposure-dependent treatment effect in patients with MET-positive gastric or oesophagogastric junction cancer., High Hepatocyte Growth Factor Receptor Expression is associated with Perihilar Cholangiocarcinoma., Results show that c-met is overexpressed in 43% of advanced esophageal squamous cell carcinoma (ESCC) and predict a worse efficacy of anti-EGFR therapy suggesting that c-Met may be an independent prognostic factor in advanced ESCC., These results suggested that the expression of the HGF/cMet pathway in gastric cancer may be a potential predictive factor for disease progression., MET-T1010I SNP may alter breast tumor pathophysiology and should be considered as a potential biomarker., The newly identified miR-34c/MET pathway provides further insights into the development and progression of nasopharyngeal carcinoma., Since c-Met has been identified as a new potential therapeutical target for treatment of hepatocellular carcinoma, damnacanthal could be potentially interesting for the treatment and/or chemoprevention of hepatocellular carcinoma, miR-93 stimulated cell proliferation, migration, and invasion through the oncogenic c-Met/PI3K/Akt pathway and also inhibited apoptosis by directly inhibiting PTEN and CDKN1A expression in human hepatocellular carcinoma., High c-Met expression levels could predict a poor prognosis in colorectal cancer patients. The c-Met status could be used to evaluate the prognosis in clinical patients., Human c-Met can promote increased survival of renal cancer cells through the regulation of HO-1 and PD-L1., Results show that overexpression of c-MET and its phosphorylation with up-regulation of VEGFR1 are associated with chemo-resistance phenotype of colon cancer., miR-206-PAX3-MET signaling is critical to GC metastasis., Expression of CD44, CD47 and c-met was upregulated in OCCC and pairwise correlation. CD44, CD47 and c-met may have synergistic effects on the development of OCCC and are prognostic factors for ovarian cancer., MACC1 overexpression predicted worse prognosis after liver resection, which was attributed to the repression of HCC cell apoptosis via a molecular mechanism in which MACC1 accelerated the activation of the HGF/c-MET/PI3K/AKT pathway, genetic association studies in populations in Ireland and Belgium, The MET receptor tyrosine kinase is overexpressed in a subset of NSCLC tumors., These results demonstrate that endometrial carcinoma stromal cells stimulate epithelial cell proliferation via the HGF/c-Met/Akt signaling pathway., evidence uncovered essential roles of CRK in invasive bladder cancer through the hepatocyte growth factor/c-Met/CRK feedback loop for epithelial-mesenchymal transition induction, EGFR, ErbB2 and MET genes are frequently amplified in gastric carcinoma., EPAS1 is a key factor in the EGFR-MET crosstalk., Review/Meta-analysis, These results demonstrated that plasma s-Met is a sensitive and reliable marker to detect c-Met overexpression in lung cancers, and it is independent of tumor volume., Results show that MET and HGF overexpression were significantly correlated in undifferentiated pleomorphic sarcomas or angiosarcomas suggesting an autocrine activation. These proteins may be potential biomarkers fro these types of sarcoma., Study describes a highly active, non-ligand-dependent mutant of MET in 6% of gliomas, which is not exposed on the cell surface and is predicted to be non-targetable with therapeutic antibodies against MET and/or hepatocyte growth factor, High expression of c-MET gene is associated with papillary thyroid carcinoma., Patients with coexpression of both receptors might benefit from cotargeting Notch-1 and c-Met., the prognostic significance of MET is limited in early stage disease. MET+/RON+ patients had higher overall recurrence rates than those with the other expression patterns, These findings indicate that the miR-1/MET pathway is a potential therapeutic target due to its crucial role in gastric cancer cell proliferation and migration., c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant chemoradiotherapy in rectal cancer., Reduced expression of miR-454 in osteosarcoma cells promoted tumor growth by targeting c-Met, thus miR-454 may be a potential therapy target for this tumor., MET gene may be useful in predicting shortened PFS and OS after Gefitinib treatment in lung adenocarcinoma. The correlation between MET gene status and clinical outcomes for EGFR-TKI should be further evaluated using large scale samples., Results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo., Results showed that cell viability decreased and apoptosis rate increased in c-MET shRNA-transfected HGF/c-MET pathway-positive MES-SA/Dx5 and MCF-7/ADR2 cell lines in a dose-dependent manner., This study suggests that IGF-1R expression could be associated with better clinical outcome in classical Hodgkin's lymphoma but is significantly associated with the expression of MET receptor., While c-MET expression is not a prognostic factor in ACC, its role as a predictive marker of benefit from MET inhibitors deserves further investigation., miR-144 suppresses GC progression by directly downregulating MET expression, which subsequently prevents activation of the pro-oncogenic Akt pathway., Data indicate that enhanced MET oncoprotein RNA expression by fusion with receptor-type tyrosine-protein phosphatase zeta (PTPRZ1)., MET overexpression is more frequent than MET high gene copy number, particularly in high grade non-small cell lung cancers, Data show that lipocalin 2 (LCN2)-induced migration occurred through activation of the Met protein/FAK protein cascade., A missense mutation of MET, encoding the hepatocyte growth factor receptor, is associated with hearing loss in humans., Study identified the G-quadruplex structure in MET promoter and showed its importance in binding to the Sp1 activator promoting tumor growth., miR-144 acts as a tumor suppressor in uveal melanoma, through inhibiting cell proliferation and migration. miR-144 might serve as a potential therapeutic target in uveal melanoma patients., MET protein overexpression and gene amplification are independent prognostic factors for OS and DFS in locoregionally advanced nasopharyngeal carcinoma, and may provide therapeutic biomarkers to identify patients in whom MET inhibitors may be beneficial., these data support the role of METex14 alterations as drivers of tumorigenesis, and identify a unique subset of patients likely to derive benefit from MET inhibitors., identification of an unprecedented role of MET in neutrophils, which suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases, we outline the key features of the MET gene, its protein product and the ligand HGF/SF, to provide an overview of this important signalling pathway and offer a summary of the relevant pathological and clinical directions of research., Met is a modulator of necrosis, able to protect cells when activated by its ligand but efficiently degraded by proteolysis when this process is engaged., Upregulation of EGFR and c-Met is associated with epithelial mesenchymal transition in response to increased matrix rigidity in pulmonary adenocarcinoma., Studied the functional role of Met signaling in dedifferentiated liposarcomas., polymorphisms of the cMET gene were found in patients with pathological complete response to Neoadjuvant chemotherapy exclusively, six different melanocytic tumours carry genomic rearrangements of MET fusing the kinase domain of MET in-frame to six different N-terminal partners, ROCK I provides better efficacy in predicting patient outcomes, compared to either tumor staging or MET expression., MET protein overexpression and MET gene amplification is associated with non-small cell lung cancer., MET levels were regulated by miR-449b in TT cells. Together, we show that reduced miR-449b levels in TT tissues may promote TC growth, through MET-mediated cell proliferation., c-Met overexpression is an adverse prognostic marker in breast cancer, except among Asian and HER-2 positive patients., The present pilot study suggests that sc-Met should be further exploited as a biomarker for monitoring of uveal melanoma., our study provided a miRNA-gene regulatory network in lung cancer metastasis and further demonstrated the roles of miR-206 and MET in this process, which enhances the understanding of the regulatory mechanism in lung cancer metastasis., our work reveals a critical relationship of Cox-2/PGE2 and HGF/MET signaling in promoting glioma cells proliferation, only miR-34a was prognostic for RFS (RR, 11.5; P = 0.027). miR-34a expression was inversely correlated with that of c-MET and CDK6 in non-small cell lung cancer , and had prognostic significance for RFS, especially in adenocarcinoma patients., c-Met identifies a population of matrix metalloproteinase 9-producing monocytes in peritumoural stroma of hepatocellular carcinoma., Ginsenoside-Rg1-induced angiogenic activities are mediated through the down-regulation of miR-23a and subsequent up-regulation of MET protein expression., MET suppresses VEGFR2 protein by inducing its endoplasmic-reticulum-associated degradation (ERAD), via intracrine VEGF action., Data show that monoclonal antibody ARGX-111 inhibits hepatocyte growth factor (HGF)-dependent proto-oncogene protein c-met (MET) activity by competing with HGF for binding to MET., Data suggest that targets of RNA interference via MIRN206 (microRNA 206) include MET (proto-oncogene c-met) and EIF4E (eukaryotic initiation factor-4E), in addition to PAX3 (paired box gene 3) and SNX2 (sorting nexin 2)., Data indicate that Met proto-oncogene protein pathway is an important target for cancer therapy., MET GCN gain and CEP7 polysomy could predict a poor outcome in CRC patients, especially CEP7 polysomy has the most powerful prognostic impact in stage II/III CRC patients., The findings suggest that the oncogenic activity of hepsin arises not only from elevated expression level but also from depletion of HAI-1, events which together trigger gain-of-function activity impacting HGF/MET signalling and epithelial cohesion, Overexpression of miR-200a in non-small lung cancer cells significantly downregulates both EGFR and c-Met levels and severely inhibits cell migration and invasion., miR-206 suppressed c-Met expression in gastric cancer and could function as a potent tumor suppressor in c-Met overexpressing tumors., c-met expression in endometrial adenocarcinoma was significantly higher than that in normal endometrial tissues., Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS., MET mutations leading to exon 14 skipping were identified in eight (22%) of 36 cases of pulmonary sarcomatoid carcinoma., TNS1, MET, and TRKC tyrosine-phosphorylated proteins are upregulated during epithelial-mesenchymal transition induced with TGF-beta, and predict the outcome in lung adenocarcinoma patients., results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease, CD24 is responsible for the recruitment of phosphorylated Met to the lipid raft domain of the cell membrane, resulting in amplification of the Met signaling cascade., In active ulcerative colitis HGFR/CDX2 expressing cells may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition., TPST1 was significantly negatively correlated with the expression of cMet in lung cancer and may be a negative prognostic biomarker of lung cancer., HGF/cMET signaling plays and important role in adrenocortical carcinoma growth and resistance to commonly used treatments., in H2170 cells and H1975 cells, simultaneous inhibition of key Wnt or mTOR pathway proteins in addition to EGFR and c-Met may be a promising strategy for overcoming EGFR and c-Met TKI resistance in NSCLC patients., HGF and its receptor, cMET, are antagonized in human lung cancer cells treated with YangZheng XiaoJi, MET activation has a role in poor response to cetuximab in patients with recurrent or metastatic head and neck cancer, miR-206 suppressed c-Met and Bcl2 expression in NSCLS and could function as a potent tumor suppressor in c-Met/Bcl2-over expressing tumors., Results indicate that proto-oncogene protein c-MET (MET) expression was significantly associated with MET amplification., analysis of ARID1A, CDH1, cMET and PIK3CA expression and target-related microRNA expression in gastric cancer, Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma., Data show that silencing of fibroblast growth factor receptors FGFR1 or FGFR2 overcomes resistance to the proto-oncogene proteins c-met (MET) inhibitor., Data show that inhibition of ATP binding cassette subfamily B member 1 (ABCB1) might be a novel therapeutic strategy for non-small cell lung cancer (NSCLC) patients with acquired resistance to proto-oncogene proteins c-met (MET) inhibitors., Data suggest that proto-oncogene protein c-met (MET )exon 14 deletion (METex14del) is a potential actionable driver mutation in gastrointestinal (GI) malignancies., Constitutive activation of MET signaling impairs myogenic differentiation of rhabdomyosarcoma and promotes its development and progression., High MET Gene Copy Number and protein expression is associated with nodal metastases in Non-Small-Cell Lung Cancer., Data reported evidence that the SNPs rs76322625 and rs41281081 in the MET 3'UTR are involved in the occurrence of non-small-cell lung cancer. They are respectively regulated by miR-335 and miR-1026 causing up-regulation of MET in patients., Results showed that c-MET Expression is increased in drug-resistant lung cancer cell lines and its inhibition reversed it confirming that activated c-MET is one of the mechanisms by which cells acquire resistance to cytotoxic anticancer drugs., High c-Met expression is associated with small cell hypercalcemic ovarian carcinoma., Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents., c-MET immunostaining in colorectal carcinoma is associated with local disease recurrence, heterogeneity of c-Met expression was widely observed in gastric cancer but was not associated with the extent of expression, BRCA1-associated DCIS did not express ER, PR or HER2, while most BRCA2-associated DCIS did express ER and PR. BRCA1- as well as BRCA2-associated DCIS had expression of HER3 and C-MET, Data indicate that oncogene c-Met was a putative target of microRNA miR-139-5p., The exonic MET variant rs11762213 is an independent predictor of adverse cancer-specific survival and time to recurrence in clear-cell renal cell carcinoma (ccRCC). Genomic analysis demonstrated that this SNP is likely causal in ccRCC., Data suggest stilbenes DIDS, H2DIDS, and derivatives as potential c-Met protein therapeutics., High PI3K p110alpha expression contributes to MET inhibitor resistance in gastric carcinoma xenografts., MET gene amplification and MET receptor activation are not sufficient to predict a positive response of non small cell lung cancers cells to a cocktail of MET and EGFR inhibitors., Data show that 11/105 patients failed all molecular analysis, Study provides evidence that Chromosome 7 gain drives MET gene copy number increase in papillary renal cell carcinoma tumors, and appears to subsequently lead to an increase in MET protein overexpression in these tumor cells., Aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone., MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression., we suggest that combinatorial therapeutic strategies with HGF and c-Met inhibitors comprise promising candidates for overcoming sorafenib resistance., Our in vitro and in vivo data suggest KRC-00715 is a potent and highly selective c-Met inhibitor which may have therapeutic potential in gastric tumor with c-Met overexpression., an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene., Since deregulation of the MET gene leads to cancer and other pathological conditions, a better understanding of the MET regulation is critical for Met-targeted therapeutics, Pre-osteoblasts stimulate migration of breast cancer cells via the HGF/MET pathway., This study suggested that GABAA receptor trafficking in the barrel cortex of Met-Emx1 mice is not sensitive to insulin., c-Met expression and activation was not found to be an independent prognostic factor in breast cancer survival outcome., Report the application of advanced quantitative fluorescence microscopy techniques to study changes in the oligomerization state of the RTK Met in response to stimulation by its endogenous ligand hepatocyte growth factor.,
OFFICIAL_GENE_SYMBOL MET,
OMIM_DISEASE Hepatocellular carcinoma, childhood type, somatic, Renal cell carcinoma, papillary, 1, familial and somatic, Deafness, autosomal recessive 97,
SP_COMMENT catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate., disease:Activation of MET after rearrangement with the TPR gene produces an oncogenic protein., disease:Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:114550]., disease:Defects in MET are a cause of hereditary papillary renal carcinoma (HPRC) [MIM:605074]; also known as papillary renal cell carcinoma 2 (RCCP2). HPRC is a form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumors. The pattern of inheritance is consistent with autosomal dominant transmission with reduced penetrance., disease:Defects in MET may be associated with gastric cancer., disease:Genetic variations in MET may be associated with susceptibility to autism type 9 (AUTS9) [MIM:611015]. Autism is a neurodevelopmental disorder characterized by disturbance in language, perception and socialization. The disorder is classically defined by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior., domain:The kinase domain is involved in SPSB1 binding., function:Receptor for hepatocyte growth factor and scatter factor. Has a tyrosine-protein kinase activity. Functions in cell proliferation, scattering, morphogenesis and survival., online information:C-MET entry, similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family., similarity:Contains 1 protein kinase domain., similarity:Contains 1 Sema domain., similarity:Contains 3 IPT/TIG domains., subunit:Heterodimer formed of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1 and GRB2. Interacts with SPSB1, SPSB2 and SPSB4 (By similarity). Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1356, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation.,