title: Down-regulating glypican-3 expression: molecular-targeted therapy for hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) prognosis is very poor, its early treatment is of the utmost importance. Glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, plays a crucial role in cell proliferation and metastasis, particularly in progression. GPC-3 mediated oncogenesis involves signaling pathways during the malignant transformation of hepatocyte carcinogenesis, with an increasing expression of GPC-3 observed from non-cancerous- to cancerous-tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. GPC-3 expression in HCC tissues or circulating blood was associated with tumor size or HBV infection. Circulation of GPC-3-mRNA was detected in HCC patients with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis. After hepatoma, cells were transfected with shRNA, GPC-3 expression or proliferation was inhibited with promoting apoptosis, cell cycle arrested in G1 phase, alteration of hepatoma cell migration and invasion behaviors with down-regulation of β-catenin, IGF-II, and VEGF, and growth of nude mice xenograft tumors was significantly suppressed with the decreases in β-catenin, p-GSK3β, and cyclinD1 expression, suggesting that GPC-3 not only is a specific biomarker for HCC diagnosis, but also is a valuable molecular-target for HCC gene therapy.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Junling
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, China. yaodf@ahnmc.com.
authors.forename: Dengfu
authors.initials: D
authors.lastname: Yao
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting / Q000379:methods / Q000639:trends*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D053673:Glypicans / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*
chemical_list: D053673:Glypicans