FOXK2激发广泛的转录抑制并阻遏缺氧反应和乳腺癌发生发展  

FOXK2 Elicits Massive Transcription Repression and Suppresses the Hypoxic Response and Breast Cancer Carcinogenesis

作　　者：Lin Shan Xing Zhou Xinhua Liu Yue Wang Dongxue Su Yongqiang Hou Na Yu Chao Yang Beibei Liu Jie Gao Yang Duan Jianguo Yang Wanjin Li Jing Liang Luyang Sun Kexin Chen Chenghao Xuan Lei Shi Yan Wang 尚永丰[2,3] 

机构地区：[1]不详 [2]中国科学院 [3]首都医科大学

出　　处：《科学新闻》2017年第4期60-60,共1页Science News

基　　金：国家自然科学基金;科技部基金支持完成

摘　　要：临床上，严重智力障碍、West综合征、Dandy-Walker畸形和并指等临床表现与转录因子FOXK2功能障碍密切相关，然而目前FOXK2的具体生物学作用尚不明确。Although clinically associated with severe developmental defects, the biological function of FOXK2 remains poorly explored. Here we report that FOXK2 interacts with transcription corepressor complexes NCoR/SMRT, SIN3A, NuRD, and REST/CoREST to repress a cohort of genes including HIF1 beta and EZH2 and to regulate several signaling pathways including the hypoxic response. We show that FOXK2 inhibits the proliferation and invasion of breast cancer cells and suppresses the growth and metastasis of breast cancer. Interestingly, FOXK2 is transactivated by ER alpha and transrepressed via reciprocal successive feedback by HIF1 beta/EZH2. Significantly, the expression of FOXK2 is progressively lost during breast cancer progression, and low FOXK2 expression is strongly correlated with higher histologic grades, positive lymph nodes, and ER alpha(-)/PR-/HER2(-) status, all indicators of poor prognosis.

关 键 词：转录因子 乳腺癌 应和 缺氧 激发 临床表现 生物学作用 智力障碍 

分 类 号：Q753[生物学—分子生物学]