|Title:||Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway||Authors:||Cheng, Wei
Lin, Tom T.C.
|Issue Date:||2008||Start page/Pages:||1319-1326||Source:||Carcinogenesis||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. ? The Author 2008. Published by Oxford University Press. All rights reserved.
|URI:||http://ntur.lib.ntu.edu.tw//handle/246246/163207||DOI:||10.1093/carcin/bgn091||SDG/Keyword:||glypican 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; Transfection
|Appears in Collections:||生化科學研究所|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.