STANDARD_NAME	BIOCARTA_MET_PATHWAY
SYSTEMATIC_NAME	M19358
COLLECTION	C2:CP:BIOCARTA
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_MET_PATHWAY
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Signaling of Hepatocyte Growth Factor Receptor
DESCRIPTION_FULL	The hepatocyte growth factor receptor, also called c-Met, is activated by HGF and stimulates proliferation of hepatocytes and other cell types. Mutated forms of the HGF receptor are associated with oncogenesis and metastasis, making the HGF receptor a potential therapeutic target for cancer drugs. Changes in cell motility, cell shape, adhesion, resistance to apoptosis, and anchorage independent growth all contribute to the role of c-Met in cancer. The HGF receptor is a heterodimer with tyrosine kinase activity and associates with a multiprotein complex involved in downstream signal transduction. The HGF receptor can associate with several different signaling systems, including src, Grb2/SOS, PI3 kinase and Gab1. One of the major substrates of the activated HGF receptor tyrosine kinase is the adaptor protein Gab1. Gab1 interacts with Crk and CrkL, two proteins with SH2 and SH3 protein interaction domains that couple to signaling further downstream. The actions of HGF on paxillin, DOCK180 and Rap1 mediated through GAB1 and other members of this complex alter cell motility. Regulation of Rho, Rac1 and CDC42 pathways in response to HGF all contribute to changes in cellular motility. Another target of the HGF receptor kinase is the focal adhesion kinase, FAK. The activation of FAK induces the formation of focal adhesions, a preliminary step to increased cell motility and tissue invasion by transformed cells, and paxillin phosphorylation may also alter cell adhesion of Met transformed cells. Src and p130cas are required for the role of FAK in HGF induced cellular transformation. HGF also blocks anoikis, the induction of apoptosis through suspension of cells, by acting on Erk and AKT kinases. This activity may contribute to anchorage independent growth of Met transformed cells. Signaling by integrins also plays a key role in the activation of tissue invasive growth by HGF. The alpha6beta4 integrin acts as a cofactor along with Meta to participate in cell growth and proliferation. In addition to altering cell adhesion, proliferation and cell motility, HGF alters cellular transcription through activation of STAT3. STAT3 activation by HGF is independent of PI3 kinase or map kinases and alters gene expression leading to changes in cellular shape. Although HGF is associated with cellular proliferation and survival, in rat liver epithelial cells HGF induces apoptosis and inhibits cell growth.
PMID	
GEOID	
AUTHORS	
CONTRIBUTOR	BioCarta
CONTRIBUTOR_ORG	BioCarta
EXACT_SOURCE	
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/human/h_metPathway.gif
SOURCE_MEMBERS	AI334281,AK021510,AK074381,AL833457,BF795331,BG682876,BM458681,BQ877285,NM_000245,NM_000314,NM_000601,NM_001010931,NM_001010932,NM_001010933,NM_001010934,NM_001010935,NM_001010942,NM_001040056,NM_001042600,NM_001100,NM_001109891,NM_001114123,NM_001127500,NM_001128620,NM_001130442,NM_001242466,NM_001251917,NM_001251918,NM_001251921,NM_001251922,NM_001257168,NM_001380,NM_002039,NM_002086,NM_002211,NM_002228,NM_002576,NM_002649,NM_002745,NM_002746,NM_002750,NM_002755,NM_002834,NM_002880,NM_002884,NM_002890,NM_003150,NM_004103,NM_005206,NM_005207,NM_005229,NM_005252,NM_005312,NM_005343,NM_005633,NM_006218,NM_007181,NM_015646,NM_016823,NM_022650,NM_030662,NM_033668,NM_080601,NM_133376,NM_138957,NM_139046,NM_139047,NM_139049,NM_139276,NM_173174,NM_173175,NM_173176,NM_176795,NM_181504,NM_181523,NM_181524,NM_198679,NM_203506,NM_207123,NM_213662
GENE_SYMBOLS	PIK3R1,PIK3CA,GAB1,SOS1,,,,,MET,PTEN,HGF,HGF,HGF,HGF,HGF,RAP1A,RAP1B,MAPK3,MAP4K1,ACTA1,MAPK3,ELK1,MET,PAK1,HRAS,PIK3R1,RAP1B,RAP1B,RAP1B,RAP1B,ELK1,DOCK1,GAB1,GRB2,ITGB1,JUN,PAK1,PIK3CG,MAPK1,MAPK3,MAPK8,MAP2K1,PTPN11,RAF1,RAP1A,RASA1,STAT3,PTK2B,CRK,CRKL,ELK1,FOS,RAPGEF1,HRAS,SOS1,PIK3CA,MAP4K1,RAP1B,CRK,RASA1,MAP2K2,ITGB1,PTPN11,ITGB1,MAPK1,MAPK8,,MAPK8,STAT3,PTK2B,PTK2B,PTK2B,HRAS,PIK3R1,PIK3R1,PIK3R1,RAPGEF1,GRB2,GAB1,STAT3
FOUNDER_NAMES