MET proto-oncogene, receptor tyrosine kinase (MET)

The MET receptor, or MET proto-oncogene, receptor tyrosine kinase, is a transmembrane protein acting as a high-affinity receptor for hepatocyte growth factor (HGF). It is a single-pass heterodimeric receptor tyrosine kinase of the Type X RTK family, composed of disulfide-linked alpha and beta chains processed from a precursor. MET plays vital roles in normal biological processes like embryogenesis, wound healing, tissue repair, and liver regeneration. Upon HGF binding, MET dimerizes and autophosphorylates, activating downstream pathways including PI3K, PLC-γ, STAT, ERK, and FAK, which regulate cell proliferation, survival, motility, migration, and angiogenesis. While normally expressed in epithelial, endothelial, and other cell types, its dysregulation, particularly through activating mutations and overexpression, is strongly implicated in various cancers including papillary renal carcinoma, hepatocellular carcinoma, and carcinomas of the stomach, lung, breast, and others. This oncogenic potential, promoting enhanced proliferation, survival, invasion, and metastasis, makes MET a significant therapeutic target in oncology. Various MET inhibitors are under development or in clinical trials for cancer treatment.

Other names

MET proto-oncogeneHGF receptorc-MET

Therapeutic drugs targeting MET function primarily by inhibiting the receptor tyrosine kinase activity or blocking HGF binding, thereby disrupting downstream signaling pathways involved in cell proliferation, survival, migration, and angiogenesis.