Hepatocyte growth factor-Mesenchymal-epithelial transition factor protein-protein interaction (HGF-MET PPI)

The Hepatocyte growth factor-Mesenchymal-epithelial transition factor (HGF-MET) protein-protein interaction is a critical signaling axis that regulates various cellular processes including proliferation, motility, and survival. HGF, a mesenchymal-derived cytokine, acts as the high-affinity ligand for the MET receptor tyrosine kinase, which is primarily expressed on epithelial cells (Source: UniProt P08581). Upon binding, HGF induces MET dimerization and autophosphorylation, triggering downstream cascades like the PI3K/AKT and Ras/MAPK pathways. In many cancers, this interaction is dysregulated through MET amplification, overexpression, or mutations, leading to uncontrolled tumor growth, metastasis, and resistance to other therapies (Source: PubMed PMC7073331). Therapeutic strategies targeting this interaction include monoclonal antibodies that block HGF binding or MET dimerization, as well as small-molecule inhibitors that target the MET kinase domain (Source: National Cancer Institute). Despite its potential, clinical challenges include managing side effects like peripheral edema and overcoming complex resistance mechanisms in the tumor microenvironment (Source: StatPearls).

Other names

HGF/c-Met axisHGF/MET signaling pathwayScatter factor/c-Met interactionHGF-MET complex

Drugs targeting the HGF-MET interaction function by either sequestering the HGF ligand, blocking the HGF binding site on the MET receptor, or inhibiting the intracellular kinase activity of MET to prevent the activation of downstream oncogenic pathways like PI3K/AKT and MAPK (Source: PubMed PMC4220520).