Targeting the HGF-cMET Axis in Hepatocellular Carcinoma

Figure 1

The hepatocyte growth factor-(HGF-) cMET axis. The hepatocyte growth factor (HGF) interacts with cMET via a paracrine signaling loop and mediates the epithelial-mesenchymal transition. Pro-HGF is secreted by stromal and mesenchymal cells and undergoes proteolytic activation into HGF. HGF binds to the MET receptor on epithelial cells and induces transautophosphorylation and binding of adaptor proteins. These provide scaffolding for recruitment of other signaling proteins and activation of signaling pathways resulting in increased invasion and motility, survival, proliferation, and stimulation of angiogenesis. Crosstalk between EGFR, cMET, and VEGF pathways is also implicated in promoting tumor survival. EGFR: epidermal growth factor receptor; FAK: focal adhesion kinase; Grb2: growth factor receptor-bound protein 2; GAB1: Grb2-associated binding protein; MEK, mitogen-activated protein kinase/ERK kinase; PI3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin; RAS: renin-angiotensin system; VEGF: vascular endothelial growth factor.