Mesenchymal–epithelial transition factor receptor (MET (c-Met))

The Mesenchymal–epithelial transition factor receptor, commonly called MET or c-Met, is a transmembrane receptor tyrosine kinase whose sole known physiological ligand is hepatocyte growth factor (HGF, also known as scatter factor). Upon HGF binding, MET dimerizes and undergoes activation loop phosphorylation (Tyr1230/1234/1235) and subsequent autophosphorylation at Tyr1349 and Tyr1356, creating docking sites that recruit adaptors (e.g., GRB2, GAB1) and enzymes (e.g., PI3K, PLCγ, SRC, SHP2), thereby activating PI3K/AKT, RAS/MAPK, JAK/STAT, SRC, and Wnt/β-catenin signaling. Physiologically, HGF/MET signaling regulates embryogenesis, organogenesis, tissue regeneration, and wound healing, promoting cell survival, proliferation, motility, and morphogenesis. Pathologically, MET is a proto-oncogene; its overexpression, amplification, or mutation (including exon 14 skipping) aberrantly activates signaling that drives tumor proliferation, invasion, EMT, angiogenesis, metastasis, and resistance to targeted therapies across multiple cancers. MET is an established therapeutic target with approved or investigational small-molecule kinase inhibitors and monoclonal antibodies that block its kinase activity or ligand-receptor interaction.

Other names

MET proto-oncogenec-MetMET receptor tyrosine kinaseHepatocyte growth factor receptor (HGFR)Mesenchymal epithelial transition factor

Small-molecule ATP-competitive inhibition of MET kinase activity, blocking phosphorylation and downstream signaling (PI3K/AKT, RAS/MAPK, STAT, SRC, Wnt/β-catenin) Monoclonal antibody antagonism/blockade of MET receptor or HGF–MET interaction, preventing ligand-induced activation and receptor dimerization