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

Abstract

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.

DOI: 10.1093/carcin/bgn091

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@article{Cheng2008Glypican3mediatedOI, title={Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway}, author={Wei Cheng and Chia-Jen Tseng and Tom T.C. Lin and I. Cheng and Hung-Wei Pan and Hey-Chi Hsu and Y. -C. Lee}, journal={Carcinogenesis}, year={2008}, volume={29}, pages={1319 - 1326} }