Insulin Receptor Substrate-1 Suppresses Transforming Growth Factor-beta 1-Mediated Epithelial-Mesenchymal Transition

	Insulin Receptor Substrate-1 Suppresses Transforming Growth Factor-beta 1-Mediated Epithelial-Mesenchymal Transition
	Shi, J; Wang, DM; Wang, CM; Hu, Y; Liu, AH; Zhang, YL; Sun, B; Song, JG
刊名	CANCER RESEARCH
	2009
卷号	69 期号:18 页码:7180-7187
通讯作者	Song, JG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,jgsong@sibs.ac.cn
英文摘要	We investigated the regulatory effect of insulin receptor substrate-1 (IRS-1) on transforming growth factor-beta 1 (TGF-beta 1)-induced epithelial-mesenchymal transition (EMT). TGF-beta 1-induced EMT and cell migration in A549 cells are associated with a decrease in IRS-1 tyrosine phosphorylation and protein levels. Tissue microarray analysis of human lung carcinoma shows a correlation between IRS-1 protein levels and E-cadherin protein levels. High IRS-1 levels coexist with high E-cadherin levels, whereas low IRS-1 levels coexist with low E-cadherin levels, implying a possibility that IRS-1 protein levels may be linked with EMT. Surprisingly, overexpression of IRS-1 in A549 cells completely blocked TGF-beta 1-induced EMT and cell migration, inhibited TGF-beta 1-mediated expression of snail and slug genes, and abolished TGF-beta 1-mediated repression of E-cadherin promoter activity. In contrast, IRS-1 knockdown by RNAi increased the expression of snail and slug genes and induced EMT. Inhibition of protein tyrosine phosphatase with sodium vanadate, which greatly increased the levels of tyrosine-phosphorylated IRS-1, suppressed TGF-beta 1-induced actin remodeling and cell morphologic changes. These results show for the first time that TGF-beta 1 induces EMT through mechanisms involving the modulation of IRS-1 signaling, and that IRS-1 functions as a critical EMT suppressor that suppresses TGF-beta 1-induced EMT via inhibition of snail and slug expression. [Cancer Res 2009;69(18):7180-7]
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	DOWN-REGULATION ; BREAST-CANCER ; CELL-DIFFERENTIATION ; I RECEPTOR ; APOPTOSIS ; IRS-1 ; PROGRESSION ; METASTASIS ; ADIPOCYTES ; (IRS)-1
收录类别	SCI
语种	英语
WOS记录号	WOS:000269954000010
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1281]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Shi, J,Wang, DM,Wang, CM,et al. Insulin Receptor Substrate-1 Suppresses Transforming Growth Factor-beta 1-Mediated Epithelial-Mesenchymal Transition[J]. CANCER RESEARCH,2009,69(18):7180-7187.
APA	Shi, J.,Wang, DM.,Wang, CM.,Hu, Y.,Liu, AH.,...&Song, JG.(2009).Insulin Receptor Substrate-1 Suppresses Transforming Growth Factor-beta 1-Mediated Epithelial-Mesenchymal Transition.CANCER RESEARCH,69(18),7180-7187.
MLA	Shi, J,et al."Insulin Receptor Substrate-1 Suppresses Transforming Growth Factor-beta 1-Mediated Epithelial-Mesenchymal Transition".CANCER RESEARCH 69.18(2009):7180-7187.