The PI3K/Akt/mTOR signaling pathway mediates insulin-like growth factor 1-induced E-cadherin down-regulation and cell proliferation in ovarian cancer cells

被引：128
作者：
Lau, Man-Tat [1 ]
Leung, Peter C. K. [1 ]
机构：
[1] Univ British Columbia, Dept Obstet & Gynecol, Child & Family Res Inst, Vancouver, BC V6H 3N1, Canada
来源：
CANCER LETTERS | 2012年 / 326卷 / 02期
基金：
加拿大健康研究院;
关键词：
E-cadherin; IGF1; Snail and Slug; GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR SNAIL; REPRESSES E-CADHERIN; FACTOR-I; CARCINOMA-CELLS; MESENCHYMAL TRANSITION; UP-REGULATION; PHOSPHATIDYLINOSITOL; 3-KINASE; TUMOR PROGRESSION; MAMMALIAN TARGET;
D O I：
10.1016/j.canlet.2012.08.016
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Insulin-like growth factor 1 (IGF1) is produced by ovarian cancer cells and it has been suggested that it plays an important role in tumor progression. In this study, we report that IGF1 treatment down-regulated E-cadherin by up-regulating E-cadherin transcriptional repressors. Snail and Slug, in human ovarian cancer cells. The pharmacological inhibition of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) suggests that PI3K/Akt/mTOR signaling is required for IGF1-induced E-cadherin down-regulation. Moreover, IGF1 up-regulated Snail and Slug expression via the PI3K/Akt/mTOR signaling pathway. Finally. IGF1-induced cell proliferation was abolished by inhibiting PI3K/Akt/mTOR signaling. This study demonstrates a novel mechanism in which IGF1 down-regulates E-cadherin expression through the activation of PI3K/Akt/mTOR signaling and the up-regulation of Snail and Slug in human ovarian cancer cells. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：191 / 198
页数：8
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