期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 714, 期 1-3, 页码 48-55出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2013.05.046
关键词
Snail; Epithelial-mesenchymal transition; GSK-3 beta; Prostate cancer
资金
- National Basic Research Program of China (973 Program) [2011CB935803]
- National Natural Science Foundation of China [81272311, 81071712]
Metastasis induced by chronic inflammation has been considered as a major challenge during cancer therapy. Epithelial mesenchymal transition (EMT) is associated with cancer invasion and metastasis promoted by pro-inflammatory cytokine TNF alpha. However, the mechanisms underlying TNF alpha-induced EMT in prostate cancer cells is not entirely clear. Here we showed that EMT induced by longstanding stimulation with TNF alpha in prostate cancer PC3 cells is mediated by up-regulation of the transcriptional repressor Snail. TNF alpha-mediated EMT was characterized by acquiring mesenchymal fusiform morphology, increasing the expression of Vimentin and decreasing the expression of E-cadherin. Exposure to TNF alpha increased the expression of transcription factor Snail via post-transcriptional regulation process and induced Snail nuclear localization in PC3 cells. Moreover, overexpressed Snail in PC3 cells induced EMT. Conversely, suppressing Snail expression abrogated TNF alpha-induced EMT, suggesting that Snail plays a crucial role in TNF alpha-induced EMT in prostate cancer cells. Finally, we showed that TNF alpha time-dependently activated NF-kappa B, AKT, ERK, p38 MAPK signaling pathways, and elevated Snail stability by activating AKT pathway that subsequently inhibited GSK-3 beta activity. Taken together, these results reveal that stabilization of Snail via AKT/GSK-3 beta signaling pathway is required for TNF alpha-induced EMT in prostate cancer cells. This study offers a better understanding of TNF alpha-induced metastasis and provides an effective therapeutic strategy for prostate cancer treatment. (c) 2013 Elsevier B.V. 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