期刊
CARCINOGENESIS
卷 37, 期 4, 页码 430-442出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgw020
关键词
-
类别
资金
- Stefanie Spielman Fund for Breast Cancer Research
- Lucius A. Wing Endowed Chair Fund
- Pelotonia Graduate Student Fellowship from The Ohio State University Wexner Medical Center and Comprehensive Cancer Center
- National Cancer Institute Cancer Center [P30 CA016058]
- Graduate Student Study Abroad Program, National Science Council, Taiwan
IL-6-NF-kappa B signaling is linked to aggressive cancer phenotypes. We report a previously unknown function of integrin-linked kinase (ILK) as a critical mediator of IL-6-NF-kappa B signaling in breast cancer cells, which provides a rationale for exploiting ILK inhibition as a therapeutic strategy.Substantial evidence has clearly demonstrated the role of the IL-6-NF-kappa 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-kappa B signaling to facilitate IL-6 production. shRNA-mediated knockdown or pharmacological inhibition of ILK disrupted this IL-6-NF-kappa 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-kappa B feedback loop and a promising therapeutic target for breast cancer.
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