This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016] CIViC Summary for MET Gene "Mesenchymal Epithelial Transition MET is a prototypical receptor tyrosine kinase. Its ligand is Hepatocyte Growth Factor (HGF). MET alterations are drivers of human cancer. Amplification and resulting overexpression has been reported in several cancers, and make the receptor's activity independent of HGF. Gene fusions also decouple kinase activity from the cell membrane and render it constitutively active. Finally, exclusion of the juxtamembrane (JM) domain of the kinase by ""skipping"" of exon 14 activates the kinase. FDA-approved selective MET inhibitors, including tepotinib and capmatinib, have shown efficacy in cancers with exon 14 skipping mutations or MET amplification."
Forensic Context
A study in rats demonstrated that the Met proto-oncogene, a hepatocyte growth factor receptor, was significantly up-regulated in liver tissue on day 7 following a 20% total body surface area burn injury [Jayaraman et al. DOI:10.1016/j.jss.2007.05.025]. This gene was identified as a key node in a relevance network analysis, indicating its involvement in processes such as hepatocyte proliferation during the long-term hepatic response to injury. A study in humans demonstrated that the MET gene, identified as a differentially expressed marker in abdominal subcutaneous adipose tissue, was down-regulated in response to a 7-day overfeeding intervention [Shea et al. DOI:10.3945/ajcn.2008.25970].