Hepatocyte growth factor – Glypican-3 interface (HGF-GPC3 interface)

The Hepatocyte growth factor – Glypican-3 (HGF-GPC3) interface is a critical protein-protein interaction that drives the progression of hepatocellular carcinoma (HCC). Glypican-3 is a cell-surface heparan sulfate proteoglycan that is highly overexpressed in HCC but absent in healthy adult liver tissue, making it an ideal therapeutic target. It functions as a co-receptor by using its heparan sulfate chains to bind HGF, which facilitates the activation of the MET (c-Met) tyrosine kinase receptor. This interaction triggers downstream signaling cascades, such as the MAPK and PI3K/AKT pathways, which promote tumor cell proliferation, migration, and invasion. Therapeutic strategies targeting this interface focus on disrupting the binding of HGF to GPC3 to halt MET-driven oncogenesis. For example, the monoclonal antibody HS20 specifically targets the heparan sulfate chains of GPC3 to block HGF interaction, showing potential in inhibiting tumor growth and metastasis in preclinical models. Because GPC3 is a tumor-specific antigen in the context of the adult liver, targeting this interface offers a high degree of selectivity for malignant cells while minimizing systemic toxicity.

Other names

HGF-GPC3 complexHGF-GPC3 interactionGPC3-HGF axisGlypican-3-Hepatocyte growth factor interaction

Inhibition of Hepatocyte growth factor (HGF) binding to the heparan sulfate chains of Glypican-3 (GPC3), thereby preventing the co-receptor-mediated recruitment and activation of the MET (c-Met) receptor and its downstream oncogenic signaling pathways.