期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 53, 期 4, 页码 769-778出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.06.014
关键词
Urothelial carcinoma; TG-interacting factor; NADPH oxidase; Reactive oxygen species; Migration; AKT
资金
- National Science Council (Taipei, Taiwan) [NSC95-2320-B-006-055-MY3, NSC98-2320-B-006-008-MY3]
Urothelial carcinoma (UC) of the bladder is the fourth most common cancer and the ninth leading cause of death from cancer among men in the United States. However, higher recurrence, resistance to therapy, and poor diagnostic/prognostic biomarkers of UC prompt us to identify novel targets to improve the clinical applications. TG-interacting factor (TGIF), a transcriptional corepressor to modulate the TGF-beta signaling, is associated with various types of human cancer. In the present study, we found that cellular migration activity, reactive oxygen species production, AKT(S473) phosphorylation, TGIF, and p67(phox) expression were higher in invasive 124 cells than in noninvasive RT4 cells. In addition, overexpression of TGIF in RT4 cells enhanced cellular migration/invasion ability: it involved NADPH oxidase 2 (Nox2)/p67(phox) complex activation, reactive oxygen species production, and AKT(S473) phosphorylation. In contrast, the migration/invasion ability of 124 cells was suppressed by the knockdown of TGIF or p67(phox), respectively. Overexpression of AKT1 could increase cellular superoxide production and invasion. Moreover, by using the PI3K/AKT inhibitor wortmannin or shRNA of AKT1, the TGIF-induced Nox activation and superoxide production were significantly inhibited. Accordingly, we suggest that PI3K/AKT signaling mediates TGIF-induced Nox2/p67(phox) complex activation and the resultant superoxide production which reinforces the PI3K/AKT signaling to promote the cellular migration/invasion ability of UC. (C) 2012 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据