Glypican-3 (GPC3) is a cell-surface glycoprotein consisting of heparan sulfate glycosaminoglycan chains and an inner protein core. It has important functions in cellular signaling including cell growth, embryogenesis, and differentiation. GPC3 has been linked to hepatocellular carcinoma and a few other cancers, however, the mechanistic role of GPC3 in cancer development remains elusive. Recent breakthroughs including the structural modeling of GPC3 and GPC3-Wnt complexes represent important steps toward deciphering the molecular mechanism of action for GPC3 and how it may regulate cancer signaling and tumor growth. A full understanding of the molecular basis of GPC3-mediated signaling requires elucidation of the dynamics of partner receptors, transducer complexes, and downstream players. Herein, we summarize current insights into the role of GPC3 in regulating cancer development through Wnt and other signaling pathways, including YAP and hedgehog cascades. We also highlight the growing body of work which underlies deciphering how GPC3 is a key player in liver oncogenesis.
Keywords: Wnt signaling; YAP signaling; antibody therapy; heparan sulfate proteoglycan; liver cancer.
Inactivation of Wnt Signaling by a Human Antibody That Recognizes the Heparan Sulfate Chains of glypican-3 for Liver Cancer TherapyW Gao et al. Hepatology 60 (2), 576-87. PMID 24492943.An antibody directed against the heparan sulfate of a proteoglycan shows efficacy in blocking Wnt signaling and HCC growth, suggesting a novel strategy for liver cancer t …
The Role of glypican-3 in Regulating Wnt in Hepatocellular CarcinomasW Gao et al. Cancer Rep 1 (1), 14-19. PMID 22563565.Glypican-3 (GPC3) is highly expressed in human hepatocellular carcinoma (HCC) and a growing body of evidence supports the role of GPC3 in HCC pathogenesis. In this review …
Glypican-3 Promotes the Growth of Hepatocellular Carcinoma by Stimulating Canonical Wnt SignalingMI Capurro et al. Cancer Res 65 (14), 6245-54. PMID 16024626.Glypican-3 (GPC3) is a heparan sulfate proteoglycan that is bound to the cell membrane by a glycosyl-phosphatidylinositol anchor. GPC3 is expressed by most hepatocellular …
Glypican-3 Targeting Immunotoxins for the Treatment of Liver CancerBD Fleming et al. Toxins (Basel) 8 (10). PMID 27669301. - ReviewHepatocellular carcinoma (HCC) is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent develo …
Glypican-3: A Marker and a Therapeutic Target in Hepatocellular CarcinomaJ Filmus et al. FEBS J 280 (10), 2471-6. PMID 23305321. - ReviewGlypican-3 (GPC3) is a member of the glypican family. Glypicans are proteoglycans that are attached to the cell surface by a glycosyl-phosphatidylinositol anchor. They re …