Mesenchymal-epithelial transition receptor (MET)

The **mesenchymal–epithelial transition receptor**—commonly referred to as **MET** or **c-Met**—is a transmembrane **receptor tyrosine kinase** primarily expressed on epithelial cells. Its natural ligand is hepatocyte growth factor (HGF), also known as scatter factor. Upon HGF binding, the receptor dimerizes and undergoes autophosphorylation at key tyrosine residues within its intracellular domain. This creates docking sites for multiple adaptor proteins that activate downstream signaling cascades such as PI3K-AKT, RAS-MAPK, STAT3, NF-kB, and WNT pathways[2][6]. These signals regulate diverse cellular processes including survival, proliferation, migration/invasion (notably during embryonic development), angiogenesis via VEGF induction[6], morphogenesis of organs like liver and kidney[1][6], stem cell maintenance[2], and tissue repair. In cancer biology, aberrant activation of the HGF/MET axis—through gene amplification/overexpression/mutation—drives tumor progression by promoting cell motility/invasion/metastasis ("proneural" glioblastoma subgroup with poor prognosis is one example)[2]. As such it is an important therapeutic target; several small-molecule inhibitors have been approved or are under investigation for cancers with dysregulated MET activity. MET's physiological importance means that therapeutic inhibition must balance efficacy against risks such as impaired organ regeneration or wound healing. Overexpression/amplification/phosphorylation status serves both prognostic/predictive biomarker roles in oncology settings.[2][6]

Other names

c-MetHepatocyte growth factor receptorHGFRMesenchymal epithelial transition factor

Drugs targeting MET typically act as tyrosine kinase inhibitors that block the phosphorylation and activation of the receptor and its downstream signaling pathways. Some monoclonal antibodies prevent ligand binding or promote receptor degradation.