FOXK1 promotes hormonally responsive breast carcinogenesis by suppressing apoptosis.

Abstract

Globally, breast cancer constitutes the predominant malignancy in women. Abnormal regulation of epigenetic factors plays a key role in the development of tumors. Anti-apoptosis is a characteristic of tumor cells. Therefore, exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy. This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive (ER+ ) breast cancer. We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions. ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites. To validate the ChIP-seq results, qChIP, western blotting, and quantitative polymerase chain reaction (qPCR) were performed. Through TUNEL assay, cell counting assay, colony formation assay, and the mouse xenograft models, the effect of FOXK1 on breast cancer progression was detected. Finally, by analyzing online databases, the correlation between FOXK1 and the survival of breast cancer patients was examined. FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway. Abnormally high expression of FOXK1 prevents the apoptosis of ER+ breast cancer cells invitro and promotes ER+ breast tumor progression invivo. Furthermore, the expression of FOXK1 is negatively correlated with the survival of ER+ breast cancer patients. FOXK1 promotes ER+ breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+ breast cancer treatment.