title: FOXK2 Elicits Massive Transcription Repression and Suppresses the Hypoxic Response and Breast Cancer Carcinogenesis.
abstract: 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 HIF1β 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 ERα and transrepressed via reciprocal successive feedback by HIF1β/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 ERα-/PR-/HER2-status, all indicators of poor prognosis.
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Lin
authors: L
authors: Shan
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Xing
authors: X
authors: Zhou
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Xinhua
authors: X
authors: Liu
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Yue
authors: Y
authors: Wang
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Dongxue
authors: D
authors: Su
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Yongqiang
authors: Y
authors: Hou
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Na
authors: N
authors: Yu
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Chao
authors: C
authors: Yang
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Beibei
authors: B
authors: Liu
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Jie
authors: J
authors: Gao
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Yang
authors: Y
authors: Duan
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Jianguo
authors: J
authors: Yang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Wanjin
authors: W
authors: Li
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Jing
authors: J
authors: Liang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Luyang
authors: L
authors: Sun
authors: Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors: Kexin
authors: K
authors: Chen
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Chenghao
authors: C
authors: Xuan
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Lei
authors: L
authors: Shi
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
authors: Yan
authors: Y
authors: Wang
authors: Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: yshang@hsc.pku.edu.cn.
authors: Yongfeng
authors: Y
authors: Shang
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C497396:ARNT protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D051858:Forkhead Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C070635:interleukin binding factor; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein