The MET gene encodes for mesenchymal-epithelial transition factor (c-MET), which is a receptor tyrosine kinase (TK) expressed on the surface of various cells.1 The gene is located on human chromosome 7 (7q21-q31) and the protein forms a heterodimer linked by the extracellular α chain and the transmembrane β chain. c-MET is a member of the MET (MNNG HOS transforming gene) family.
Hepatocyte growth factor (HGF) is the ligand for c-MET and binding initiates a series of intracellular signals that play a role in normal biological functions in humans.1 These signals mediate embryogenesis, tissue regeneration, nerve and muscle formation, and wound healing. In cancer cells, however, abnormal c-MET activation promotes liver, lung, colon, breast, pancreatic, ovarian, prostate, and gastric carcinoma development and progression.
In addition, HGF/c-MET binding can stimulate signaling pathways in tumor cells such as PI3K/AKT, JAK/STAT, Ras/MAPK, SRC, Wnt/β-catenin, and others. Mutations, overexpression, and amplification in c-MET are demonstrated in a variety of human tumor types. Overexpression of c-MET is also associated with a poor prognosis in cancer patients.
