FOXK2 Elicits Massive Transcription Repression and Suppresses the Hypoxic Response and Breast Cancer Carcinogenesis.
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.
Mesh Terms:
Animals, Aryl Hydrocarbon Receptor Nuclear Translocator, Breast Neoplasms, Cell Hypoxia, Cell Line, Tumor, Cell Proliferation, Down-Regulation, Enhancer of Zeste Homolog 2 Protein, Estrogen Receptor alpha, Female, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasm Invasiveness, Prognosis, Signal Transduction, Transcription, Genetic
Animals, Aryl Hydrocarbon Receptor Nuclear Translocator, Breast Neoplasms, Cell Hypoxia, Cell Line, Tumor, Cell Proliferation, Down-Regulation, Enhancer of Zeste Homolog 2 Protein, Estrogen Receptor alpha, Female, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasm Invasiveness, Prognosis, Signal Transduction, Transcription, Genetic
Cancer Cell
Date: Nov. 14, 2016
PubMed ID: 27773593
View in: Pubmed Google Scholar
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