Find HGF Products Interaction Network for HGF HGF Details

Related Pathways Hepatic Fibrosis / Hepatic Stellate Cell Activation FGF Signaling Macropinocytosis View All Pathways

Synonyms: C230052L06Rik, F-TCF, HEPATOCYTE GROWTH FACTOR, HGF, HGF/SF, HGFB, HPTA, NK1, NK2, SF, SF/HGF

HGF Pathway

Hepatocyte Growth Factor (HGF)/Scatter Factor (SF) is a mesenchymally derived heparin-binding glycoprotein involved in development, homeostasis and regeneration of a variety of normal tissues. It is also associated with many types of cancer. HGF mRNA is found in fibroblasts, smooth muscle cells, mast cells, macrophages, endothelial cells, leukocytes, and megakaryocytes. HGF is secreted as a biologically inactive precursor (pro-HGF) that is site-specifically activated by proteolytic cleavage into alpha and beta subunits joined by a disulfide bond. HGF is a mediator of mesenchymal-epithelial interactions leading to proliferation and morphogenesis of epithelial cells that supports parenchymal organogenesis of the liver, lung, intestines, kidneys and other organs.

HGF stimulates mitogenic, motogenic (including metastogenesis) and morphogenic effects on epithelial and endothelial cells via is receptor, Met. Met is a proto-oncogene that when mutated can transform a variety of cell types. The Met receptor is a heterodimer consisting of an extracellular alpha chain and a trans-membrane beta chain which is a tyrosine kinase. Met is widely expressed by epithelial and endothelial cells. It is expressed by melanocytes, chondrocytes, skeletal muscle, hematopoietic, lymphoid, and neural cells.

The activation of Met by HGF binding is linked to cell growth and survival, including the avoidance of anoikis which is apoptosis induced by insufficient association with cell-matrix, through activation of both the PI3-kinase/PDK/Akt and the Ras/Raf/MEK/ERK pathways and to cell mobility and cytoskeletal organization via activation of the Rho-GTPases, Rho, Rac and CDC42. Activation of Met tyrosine kinase also activates phospholipase C which results in the elevation of intracellular calcium and activation of conventional and novel protein kinase C pathways.

HGF and Met have been associated with progression, invasiveness and metastasis in a number of cancer types. Met is expressed in a wide variety of carcinomas, musculoskeletal and soft tissue sarcomas, glioblastomas/astrosarcomas, and several hematopoietic malignancies. HGF Met signaling is a major target for cancer therapeutics development.