STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion

被引：101
作者：
Cho, Kyung Hwa [1 ]
Jeong, Kang Jin [1 ]
Shin, Shang Cheul [2 ]
Kang, Jaeku [1 ]
Park, Chang Gyo [1 ]
Lee, Hoi Young [1 ]
机构：
[1] Konyang Univ, Dept Pharmacol, Coll Med, Myunggok Med Res Inst, Taejon 302718, South Korea
[2] Konyang Univ, Dept Dent, Coll Med, Myunggok Med Res Inst, Taejon 302718, South Korea
来源：
CANCER LETTERS | 2013年 / 336卷 / 01期
基金：
新加坡国家研究基金会;
关键词：
TGF-beta; 1; TWIST1; STAT3; HIF-1; alpha; Prostate cancer cell invasion; EPITHELIAL-MESENCHYMAL TRANSITION; UP-REGULATION; HIF-1-ALPHA;
D O I：
10.1016/j.canlet.2013.04.024
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
TGF-beta 1 induces epithelial-mesenchymal transition (EMT) to stimulate cancer cell progression, and TWIST1 is a critical regulator of EMT. In the present study, we determined the underlying mechanisms of TGF-beta 1 -induced TWIST1 expression and its effect on prostate cancer cell invasion. TGF-beta 1 stimulated STAT3 phosphorylation and HIF-1a expression. Silencing either STAT3 or HIF-1 alpha efficiently attenuated TGF-beta 1-induced TVVIST1 expression. Further ectopic expression of a dominant negative mutant of STAT3 reduced TGF-01-induced TWIST1 expression. In addition, STAT3 and HIF-1 alpha up-regulated TWIST1 expression by direct binding to a TWIST1 promoter. Strikingly, STAT3 also enhanced TGF-beta 1 -induced TWIST1 expression through HIF-1 alpha stabilization. Collectively, we demonstrate a mechanistic cascade of TGF-beta 1 up-regulating STAT3 activation and HIF-1 alpha stabilization and subsequent TWIST1 expression, leading to prostate cancer invasion. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：167 / 173
页数：7
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