Integrin-linked kinase as a novel molecular switch of the IL-6-NF-{kappa}B signaling loop in breast cancer

Substantial evidence has clearly demonstrated the role of the IL-6-NF-B 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-B signaling to facilitate IL-6 production. shRNA-mediated knockdown or pharmacological inhibition of ILK disrupted this IL-6-NF-B 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-B feedback loop and a promising therapeutic target for breast cancer.

Source: Carcinogenesis - March 23, 2016 Category: Cancer & Oncology Authors: 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. Tags: Original Manuscript Source Type: research