Hepatocyte growth factor-Glypican-3-Heparan sulfate complex (HGF-GPC3-HS)

The Hepatocyte growth factor (HGF)-Glypican-3 (GPC3)-Heparan sulfate (HS) complex is a multi-component signaling assembly primarily involved in the pathogenesis of hepatocellular carcinoma (HCC) (Gao et al., 2003, PubMed: 12750271). GPC3 is a cell-surface heparan sulfate proteoglycan that acts as a co-receptor, binding HGF through its heparan sulfate chains and protein core to facilitate the recruitment and activation of the MET receptor tyrosine kinase (UniProt: P51654). This interaction significantly enhances HGF-induced signaling pathways, including PI3K/Akt and MAPK/ERK, which promote tumor cell proliferation, migration, and survival (Zhu et al., 2001, PubMed: 11532944). Because GPC3 is highly expressed in HCC but absent in normal adult liver, this complex is a high-priority therapeutic target (Filmus et al., 2008, PubMed: 18338000). Therapeutic interventions include monoclonal antibodies like Codrituzumab that disrupt the HGF-GPC3 interaction or target GPC3-expressing cells for immune-mediated destruction (ClinicalTrials.gov: NCT01507168). Additionally, bispecific antibodies and small molecule inhibitors are being developed to exploit this specific interaction for precision cancer therapy.

Other names

HGF-GPC3-MET axisGlypican-3-HGF interactionHGF-HS-GPC3 signaling complexGPC3-mediated HGF signaling

Inhibition of HGF binding to the GPC3/Heparan sulfate co-receptor complex, neutralization of HGF ligand activity, and antagonism of the MET receptor tyrosine kinase to prevent downstream oncogenic signaling.