DAVID Gene Report
2858889
met proto-oncogene (hepatocyte growth factor receptor) Related Genes Homo sapiens
REFSEQ_MRNA
NM_000245 ,
UNIGENE
Hs.132966 ,
OMIM_DISEASE
Autism, suseptibility to, 9 ,
Hepatocellular carcinoma, childhood type ,
Renal cell carcinoma, papillary, familial and sporadic ,
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 1B (AUTS1B) [MIM:608636]. 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.,
function:Receptor for hepatocyte growth factor and scatter factor. Has a tyrosine-protein kinase activity.,
similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family.,
similarity:Contains 1 Sema domain.,
similarity:Contains 1 protein kinase domain.,
similarity:Contains 3 IPT/TIG domains.,
subcellular location:Membrane; Single-pass type I membrane protein.,
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.,
UNIREF100_ID
UniRef100_P08581 ,
UniRef100_Q14825 ,
UniRef100_Q59EB3 ,
UNIPROT_ID
MET_HUMAN ,
Q14825_HUMAN ,
Q59EB3_HUMAN ,
Q9UEJ3_HUMAN ,
Q9UMU9_HUMAN ,
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 ,
Findings disclose a cross-talk between the COX-2/PGE(2)/EP(1) and EGFR/c-Met signaling pathways that coordinately regulate human hepatocellular carcinoma cell invasion. ,
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 ,
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 ,
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 ,
The tumor suppressor activity of GPx3 seems to relate to its ability to suppress the expression of c-met. ,
ENTREZ_GENE_ID
4233 ,
EC_NUMBER
2.7.10.1 ,
CYTOBAND
7q31,
PIR_SUMMARY
Receptor for hepatocyte growth factor and scatter factor. Has a tyrosine-protein kinase activity.,
PIR_NREF_ID
NF00075350,
NF00077422,
NF00083222,
NF00085297,
NF00110304,
NF00120818,
NF00135840,
NF00138731,
NF01686017,
NF01686981,
NF02397384,
CHROMOSOME
7,
GENPEPT_ACCESSION
AAA59585 ,
AAA59589 ,
AAA59590 ,
AAA59591 ,
AAA68513 ,
AAB54047 ,
AAB60323 ,
AAC60383 ,
AAF66137 ,
AAH27979 ,
AAI30421 ,
ALT_SEQ ,
BAD93135 ,
CAB56793 ,
EAL24359 ,
EAW83507 ,
EAW83508 ,
EAW83509 ,
EAW83510 ,
EAW83511 ,
Genomic_DNA ,
mRNA ,
ENTREZ_GENE_SUMMARY
The proto-oncogene MET product is the hepatocyte growth factor receptor and encodes tyrosine-kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor. Various mutations in the MET gene are associated with papillary renal carcinoma.,
GENE_SYMBOL
MET ,
REFSEQ_PROTEIN
NP_000236 ,
GENE_NAME
HGF receptor,
HGF/SF receptor,
Hepatocyte growth factor receptor,
Hepatocyte growth factor receptor (Fragment),
Hepatocyte growth factor receptor precursor,
Hepatocyte growth factor receptor precursor (EC 2.7.10.1) (HGF receptor) (Scatter factor receptor) (SF receptor) (HGF/SF receptor) (Met proto-oncogene tyrosine kinase) (c-Met),
MET protein,
MET protein (Fragment),
Met proto-oncogene tyrosine kinase,
Met proto-oncogene variant,
Proto-oncogenic met protein,
Proto-oncogenic met protein (Fragment),
SF receptor,
Scatter factor receptor,
c-Met,
met proto-oncogene (hepatocyte growth factor receptor),
Download File
