C-MET

C-MET, also known as MET proto-oncogene, receptor tyrosine kinase, is a protein that in humans is encoded by the MET gene. This gene is located on chromosome 7q31 and is involved in various cellular processes, including growth, survival, and metastasis.

Structure

The MET protein is a receptor tyrosine kinase that consists of an extracellular domain, a transmembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain is responsible for binding to its ligand, Hepatocyte Growth Factor (HGF), also known as scatter factor.

Function

C-MET plays a crucial role in embryonic development, organ regeneration, and wound healing. It is primarily activated by binding to HGF, which leads to receptor dimerization and autophosphorylation of tyrosine residues in the intracellular domain. This activation triggers several downstream signaling pathways, including the PI3K/AKT pathway, RAS/MAPK pathway, and STAT pathway, which are involved in cell proliferation, survival, and motility.

Clinical Significance

Aberrant activation of C-MET has been implicated in various types of cancer, including lung cancer, gastric cancer, and renal cell carcinoma. Overexpression, gene amplification, and mutations in the MET gene can lead to uncontrolled cell growth and metastasis. As a result, C-MET is a target for cancer therapy, and several MET inhibitors are currently being developed and tested in clinical trials.

Research and Therapeutics

Research on C-MET has led to the development of targeted therapies aimed at inhibiting its activity. These include small molecule inhibitors, monoclonal antibodies, and HGF antagonists. Some of the MET inhibitors that have been approved or are in clinical trials include crizotinib, cabozantinib, and tepotinib.

Also see

• Hepatocyte Growth Factor
• Receptor Tyrosine Kinase
• Signal Transduction
• Oncogene
• Cancer Therapy