HGF

Hepatocyte growth factor (HGF), also known historically as scatter factor, is a pleiotropic protein that acts as a growth, motility, and morphogenic factor for a wide range of cells. It is primarily produced by mesenchymal cells and secreted as an inactive single-chain precursor. Activation proteolytically converts HGF into its active, heterodimeric form, composed of an alpha and a beta chain. HGF exerts its effects by signaling through the Met receptor, a receptor tyrosine kinase encoded by the MET gene, which is expressed on epithelial, endothelial, and certain other cell types.

Upon HGF binding, Met dimerizes and undergoes autophosphorylation, triggering downstream signaling pathways such as RAS-ERK, PI3K-AKT, and STAT. These pathways promote cell proliferation, survival, migration, and morphogenesis. HGF–Met signaling plays a central role in embryonic development of organs including the liver and kidneys, and it continues to regulate tissue regeneration, wound healing, angiogenesis, and branching morphogenesis in adult tissues. HGF can influence cell scattering and motility, contributing to morphogenic processes during organ formation and repair.

Regulation of HGF activity involves its production in a paracrine manner and the controlled proteolytic activation of the latent single-chain precursor by proteases such as HGF activator (HGFA) and plasmin. HGF also interacts with heparan sulfate proteoglycans, which modulate its bioavailability and distribution in the extracellular matrix.

Clinical significance of the HGF–Met axis includes its involvement in cancer progression and metastasis, as well as in fibrotic diseases and tissue repair. Dysregulation of HGF or MET can contribute to tumor growth and dissemination, making the HGF–Met signaling pathway a focus of therapeutic research, with approaches aiming to inhibit Met activation or HGF–Met signaling.