Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer

En Chi Hsu, Samuel K. Kulp, Han Li Huang, Huang Ju Tu, Min Wu Chao, Yu Chou Tseng, Ming Chen Yang, Santosh B. Salunke, Nicholas J. Sullivan, Wen Chung Chen, Jianying Zhang, Che Ming Teng, Wen Mei Fu, Duxin Sun, Max S. Wicha, Charles L. Shapiro, Ching Shih Chen

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

Substantial evidence has clearly demonstrated the role of the IL-6-NF-κB signaling loop in promoting aggressive phenotypes in breast cancer. However, the exact mechanism by which this inflammatory loop is regulated remains to be defined. Here, we report that integrin-linked kinase (ILK) acts as a molecular switch for this feedback loop. Specifically, we show that IL-6 induces ILK expression via E2F1 upregulation, which, in turn, activates NF-κB signaling to facilitate IL-6 production. shRNAmediated knockdown or pharmacological inhibition of ILK disrupted this IL-6-NF-κB signaling loop, and blocked IL-6-induced cancer stem cells in vitro and estrogen-independent tumor growth in vivo. Together, these findings establish ILK as an intermediary effector of the IL-6-NF-κB feedback loop and a promising therapeutic target for breast cancer.

原文英語
頁(從 - 到)430-442
頁數13
期刊Carcinogenesis
37
發行號4
DOIs
出版狀態已發佈 - 十月 29 2015
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Cancer Research

引用此

Hsu, E. C., Kulp, S. K., Huang, H. L., Tu, H. J., Chao, M. W., Tseng, Y. C., Yang, M. C., Salunke, S. B., Sullivan, N. J., Chen, W. C., Zhang, J., Teng, C. M., Fu, W. M., Sun, D., Wicha, M. S., Shapiro, C. L., & Chen, C. S. (2015). Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer. Carcinogenesis, 37(4), 430-442. https://doi.org/10.1093/carcin/bgw020