1. Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer
- Author
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Jianying Zhang, Ming Chen Yang, Che-Ming Teng, Samuel K. Kulp, Max S. Wicha, Wen Chung Chen, Ching-Shih Chen, Huang Ju Tu, Santosh B. Salunke, Han Li Huang, En-Chi Hsu, Yu Chou Tseng, Duxin Sun, Nicholas J. Sullivan, Charles L. Shapiro, Min Wu Chao, and Wen-Mei Fu
- Subjects
0301 basic medicine ,Cancer Research ,Gene knockdown ,biology ,Chemistry ,Effector ,Kinase ,Interleukin-6 ,NF-kappa B ,Breast Neoplasms ,Original Manuscript ,General Medicine ,Protein Serine-Threonine Kinases ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Downregulation and upregulation ,Cancer stem cell ,embryonic structures ,biology.protein ,E2F1 ,Humans ,Integrin-linked kinase ,Signal transduction ,Signal Transduction - Abstract
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. shRNA-mediated 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.
- Published
- 2015