Proto-oncogene protein c-Met receptor tyrosine kinase (c-Met)

The proto-oncogene protein c-Met is a cell surface **receptor tyrosine kinase** encoded by the MET gene on chromosome 7q31. It is produced as a single-chain precursor that is cleaved into an extracellular α-subunit and a transmembrane β-subunit linked by disulfide bonds. The primary endogenous ligand is hepatocyte growth factor (**HGF**), also known as scatter factor or tumor cytotoxic factor. Upon HGF binding, c-Met undergoes dimerization and autophosphorylation on specific intracellular tyrosines—creating docking sites for downstream effectors such as PI3K/AKT/mTOR and RAS/MAPK pathways—which drive cellular processes including proliferation, survival/anti-apoptosis, motility/invasion ("scattering"), morphogenesis during development/regeneration/wound healing. Aberrant activation of the HGF/c-MET pathway—via overexpression/amplification/mutation—is implicated in oncogenic transformation across multiple solid tumors where it promotes tumorigenesis/metastasis/resistance to therapy. As such it is considered a validated therapeutic target with several approved or investigational small-molecule inhibitors available for clinical use or under study.

Other names

METHepatocyte growth factor receptor (HGFR)Scatter factor receptorTumor cytotoxic factor receptorMET proto-oncogene, receptor tyrosine kinase

Drugs targeting this molecule typically act as **small molecule inhibitors** that block the ATP-binding site of the c-Met tyrosine kinase domain. This inhibits autophosphorylation and downstream signaling pathways involved in cell proliferation and survival. Some agents may also block ligand binding or dimerization.