Hepatocyte growth factor receptor (HGFR) (MET)

Hepatocyte growth factor receptor (HGFR), also known as c-Met, is a transmembrane receptor tyrosine kinase that is essential for tissue homeostasis and repair (UniProt: P08581). It is the specific receptor for hepatocyte growth factor (HGF), and their interaction triggers signaling pathways such as RAS/MAPK and PI3K/AKT that promote cell survival and motility (PubMed: 22566020). In the field of virology and gene therapy, HGFR is recognized as the key co-receptor for Adeno-associated virus serotype 3b (AAV3b), which explains the high tropism of this viral vector for human hepatocytes (PubMed: 20444891). Aberrant MET signaling, often caused by gene amplification or mutations like MET exon 14 skipping, is a significant driver in several malignancies, particularly non-small cell lung cancer and hepatocellular carcinoma (PubMed: 32459914). Consequently, HGFR is a major therapeutic target for several FDA-approved kinase inhibitors, including capmatinib and tepotinib. Beyond oncology, the AAV3b-HGFR interaction is a critical component in the design of liver-directed gene therapies, allowing for precise cellular entry and transduction.

Other names

c-MetTyrosine-protein kinase MetHGF receptorScatter factor receptorMET

Small-molecule inhibition of the MET tyrosine kinase domain or monoclonal antibody-mediated blockade of the HGF-MET interaction.