BRD4
溴尿嘧啶
癌症研究
乳腺癌
表观遗传学
癌症
组蛋白
基因敲除
三阴性乳腺癌
Notch信号通路
生物
染色质
信号转导
细胞生物学
遗传学
细胞凋亡
基因
作者
Guillaume P. Andrieu,Anna H. Tran,Katherine J. Strissel,Gerald V. Denis
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2016-11-14
卷期号:76 (22): 6555-6567
被引量:104
标识
DOI:10.1158/0008-5472.can-16-0559
摘要
The bromodomain and extraterminal (BET) proteins are epigenetic "readers" of acetylated histones in chromatin and have been identified as promising therapeutic targets in diverse cancers. However, it remains unclear how individual family members participate in cancer progression and small molecule inhibitors such as JQ1 can target functionally independent BET proteins. Here, we report a signaling pathway involving BRD4 and the ligand/receptor pair Jagged1/Notch1 that sustains triple-negative breast cancer migration and invasion. BRD4, but not BRD2 or BRD3, regulated Jagged1 expression and Notch1 signaling. BRD4-selective knockdown suppressed Notch1 activity and impeded breast cancer migration and invasion. BRD4 was required for IL6-stimulated, Notch1-induced migration and invasion, coupling microenvironment inflammation with cancer propagation. Moreover, in patients, BRD4 and Jagged1 expression positively correlated with the presence of distant metastases. These results identify a BRD4/Jagged1/Notch1 signaling pathway that is critical for dissemination of triple-negative breast cancer. Cancer Res; 76(22); 6555-67. ©2016 AACR.
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