Cheng, WeiWeiChengTseng, Chia-JenChia-JenTsengLin, Tom T.C.Tom T.C.LinCheng, I.I.ChengPan, Hung-WeiHung-WeiPanHsu, Hey-ChiHey-ChiHsuLee, Yu-MayYu-MayLee2009-08-052018-07-062009-08-052018-07-062008http://ntur.lib.ntu.edu.tw//handle/246246/163207Glypican-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. ? The Author 2008. Published by Oxford University Press. All rights reserved.application/pdf640494 bytesapplication/pdfen-US[SDGs]SDG3glypican 3; mitogen activated protein kinase; proline; somatomedin; somatomedin B; somatomedin C receptor; amino terminal sequence; article; cancer cell; cell strain; cell strain 3T3; cell strain HuH 7; controlled study; gene overexpression; human; human cell; liver carcinogenesis; liver cell carcinoma; phenotype; priority journal; protein binding; protein interaction; protein phosphorylation; signal transduction; Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Transformation, Neoplastic; Extracellular Signal-Regulated MAP Kinases; Glypicans; Hela Cells; Humans; Insulin-Like Growth Factor II; Liver Neoplasms; Mice; NIH 3T3 Cells; Phosphorylation; Receptor, IGF Type 1; Signal Transduction; Transfection10.1093/carcin/bgn091http://ntur.lib.ntu.edu.tw/bitstream/246246/163207/1/13.pdf