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FOXK2 ChIP sequencing in non-treated MCF-7 cells

ABSTRACT: Although clinically associated with severe intellectual disability, West syndrome, Dandy-Walker malformation, and syndactyly, the biological function of FOXK2 remains poorly explored. Here we report that FOXK2 acts as a transcription repressor. Strikingly, FOXK2 interacts with multiple transcription corepressor complexes including NCoR/SMRT, SIN3A, NuRD, and REST/CoREST. FOXK2 assembles these transcription programs to repress a cohort of genes including HIF1 and EZH2 and to regulate several signaling pathways including the hypoxic response that is critically implicated in tumor development and progression. We showed that FOXK2 inhibits the proliferation and invasion of breast cancer cells in vitro and suppresses the growth and metastasis of breast cancer in vivo. Interestingly, FOXK2 is transactivated by ERand transrepressed via reciprocal successive feedback by HIF1/EZH2. Significantly, the expression of FOXK2 is progressively lost during breast cancer progression, leading to elevated expression of EZH2, an eminent feature of aggressive breast cancer. Indeed, the expression of FOXK2 is inversely correlated with that of EZH2 and HIF1in breast carcinomas, and low FOXK2 expression is strongly correlated with higher histologic grades, positive lymph nodes, and ER/PR/Her2 status, all indicators of poor prognosis. Our experiments revealed that FOXK2 is massively involved in transcription repression, providing a molecular basis for the understanding of the mechanistic action of FOXK2. Our study identified the ER-FOXK2-HIF1/EZH2 axis in breast cancer progression, supporting the pursuit of these molecules as therapeutic targets for breast cancer intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84241 | GEO | 2016/11/08

REPOSITORIES: GEO

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