Journal Article

Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway

Wei Cheng, Chia-Jen Tseng, Tom T.C. Lin, I. Cheng, Hung-Wei Pan, Hey-Chi Hsu and Yu-May Lee

in Carcinogenesis

Volume 29, issue 7, pages 1319-1326
Published in print July 2008 | ISSN: 0143-3334
Published online April 2008 | e-ISSN: 1460-2180 | DOI:

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Glypican-3 (gpc3) is the gene responsible for Simpson-Golabi-Behmel overgrowth syndrome. Previously, we have shown that GPC3 is overexpressed in hepatocellular carcinoma (HCC). In this study, we demonstrated the mechanisms for GPC3-mediated oncogenesis. Firstly, GPC3 overexpression in NIH3T3 cells gave to cancer cell phenotypes including growing in serum-free medium and forming colonies in soft agar, or on the other way, GPC3 knockdown in HuH-7 cells decreased oncogenecity. We further demonstrated that GPC3 bound specifically through its N-terminal proline-rich region to both Insulin-like growth factor (IGF)-II and IGF-1R. GPC3 stimulated the phosphorylation of IGF-1R and the downstream signaling molecule extracellular signal-regulated kinase (ERK) in an IGF-II-dependent way. Also, GPC3 knockdown in HCC cells decreased the phosphorylation of both IGF-1R and ERK. Therefore, GPC3 confers oncogenecity through the interaction between IGF-II and its receptor, and the subsequent activation of the IGF-signaling pathway. This data are novel to the current understanding of the role of GPC3 in HCC and will be important in future developments of cancer therapy.

Journal Article.  5019 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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