https://scholars.lib.ntu.edu.tw/handle/123456789/564578
標題: | Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer | 作者: | 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. WEN-MEI FU Sun D. Wicha M.S. Shapiro C.L. Chen C.-S. |
公開日期: | 2015 | 卷: | 37 | 期: | 4 | 起(迄)頁: | 430-442 | 來源出版物: | Carcinogenesis | 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. ? The Author 2016. Published by Oxford University Press. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/564578 | ISSN: | 1433334 | DOI: | 10.1093/carcin/bgw020 | SDG/關鍵字: | cyclin D1; cyclin dependent kinase 2; doxycycline; immunoglobulin enhancer binding protein; integrin linked kinase; interleukin 6; lentivirus vector; messenger RNA; short hairpin RNA; STAT3 protein; transcription factor E2F1; immunoglobulin enhancer binding protein; integrin-linked kinase; interleukin 6; protein serine threonine kinase; animal experiment; animal model; animal tissue; Article; breast cancer; cancer gene therapy; cancer inhibition; cancer stem cell; cancer survival; cell proliferation; controlled study; cytokine production; cytokine release; ectopic expression; enzyme activation; enzyme active site; feedback system; female; gene overexpression; gene silencing; gene switching; human; human cell; human tissue; immunohistochemistry; MCF 7 cell line; molecular switch; mouse; nonhuman; nonviral gene therapy; priority journal; protein expression; protein phosphorylation; recurrence free survival; signal transduction; transactivation; upregulation; viral gene delivery system; breast tumor; metabolism; physiology; Breast Neoplasms; Humans; Interleukin-6; NF-kappa B; Protein-Serine-Threonine Kinases; Signal Transduction |
顯示於: | 藥理學科所 |
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