FOXK2 Elicits Massive Transcription Repression and Suppresses the Hypoxic Response and Breast Cancer Carcinogenesis
Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels la protéine FOXK2 réprime la croissance et le processus métastatique d'un cancer du sein
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? 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 HIF1?/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.