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. 2020 Dec;4(4):168-172.
doi: 10.1016/j.livres.2020.11.003. Epub 2020 Nov 11.

Glypican-3: A molecular marker for the detection and treatment of hepatocellular carcinoma☆

Tsung-Chieh Shih  1 , Lijun Wang  2 , Hsiao-Chi Wang  3 , Yu-Jui Yvonne Wan  2
Affiliations

Glypican-3: A molecular marker for the detection and treatment of hepatocellular carcinoma☆

Tsung-Chieh Shih et al. Liver Res. 2020 Dec.

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor with a fairly poor prognosis (5-year survival of less than 50%). Using sorafenib, the only food and drug administration (FDA)-approved drug, HCC cannot be effectively treated; it can only be controlled at most for a couple of months. There is a great need to develop efficacious treatment against this debilitating disease. Glypican-3 (GPC3), a member of the glypican family that attaches to the cell surface by a glycosylphosphatidylinositol anchor, is overexpressed in HCC cases and is elevated in the serum of a large proportion of patients with HCC. GPC3 expression contributes to HCC growth and metastasis. Furthermore, several different types of antibodies targeting GPC3 have been developed. The aim of this review is to summarize the current literatures on the GPC3 expression in human HCC, molecular mechanisms of GPC3 regulation and antibodies targeting GPC3.

Keywords: Glypican-3 (GPC3); Hepatocellular carcinoma (HCC); Wnt signaling.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no conflict of interest.

Figures

Fig. 1.
Fig. 1.. The structure of GPC3 protein.
GPC3 consists of a core protein and a heparan sulfate chain. It binds to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. GPC3 has a cleavage site between Arg358 and Ser359 for Furin protease. Cleavage by furin results in a 40-kDa N-terminal subunit and a 30-kDa C-terminal subunit. These two subunits can be linked by a disulfide bond. Two heparan sulfate (HS) side chains occur near the C-terminal of GPC3 (Ser495 and Ser509). Ser560 of GPC3 inserts into the lipid bilayer and anchors the protein to the bilayer by phosphatidylinositol. GPC3 can be released from the cell surface into the extracellular environment after cleavage by Notum, an extracellular lipase that releases GPC3 by cleaving the GPI anchor. Fig. 1 is created using tools in BioRender.com. Abbreviations: GPC3, Glypican-3; GPI, glycosylphosphatidylinositol; HS, heparan sulfate.
Fig. 2.
Fig. 2.. GPC3 and Wnt cell signaling.
GPC3 forms a complex with Wnt and activates Wnt signaling leading to the HCC growth. Fig. 2 is created using tools in Fig. 1 is created using tools in BioRender.com. Abbreviations: GPC3, Glypican-3; HS, heparan sulfate; TCF/LEF, T-cell factor/lymphoid enhancer factor.
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention. Wide-ranging online data for epidemiologic research (WONDER). Underlying cause of death output based on the Detailed Mortality File. https://wonder.cdc.gov/. Accessed Aug 2, 2020.
    1. Villanueva A Hepatocellular carcinoma. N Engl J Med. 2019;380:1450–1462. - PubMed
    1. Ronot M, Bouattour M, Wassermann J, et al. Alternative Response Criteria (Choi, European association for the study of the liver, and modified Response Evaluation Criteria in Solid Tumors [RECIST]) versus RECIST 1.1 in patients with advanced hepatocellular carcinoma treated with sorafenib. Oncologist. 2014;19:394–402. - PMC - PubMed
    1. Li B, Liu H, Shang HW, Li P, Li N, Ding HG. Diagnostic value of glypican-3 in alpha fetoprotein negative hepatocellular carcinoma patients. Afr Health Sci. 2013;13:703–709. - PMC - PubMed
    1. Guo M, Zhang H, Zheng J, Liu Y. Glypican-3: a new target for diagnosis and treatment of hepatocellular carcinoma. J Cancer. 2020;11:2008–2021. - PMC - PubMed