The Regulation of Elf5 Methylation in Breast Cancer Progression

Abstract

Breast cancer is a major health concern, affecting hundreds of thousands of people. Metastasis, or the spread of tumor cells to organs other than the primary site, is of particular concern as it is responsible for a vast majority of breast cancer deaths. The transcription factor E74-like factor 5 (Elf5) is a master regulator of alveolar development in the breast and has been shown to inhibit metastasis by regulating the transcription of Snail2. However, little is known about how Elf5 is regulated in the context of breast cancer and whether its role varies across different subtypes of breast cancer. DNA methylation is a promising candidate for Elf5 regulation due to its correlation with Elf5 expression in the normal development context and in other cancers. In this study, we find a negative correlation between Elf5 expression and methylation across both the molecular subtypes and ER status of breast cancer. Moreover, we show through functional experiments that demethylation, and subsequent upregulation, of Elf5 eliminates the metastatic phenotype of breast cancer cells. Finally, we identify Tet1 as a potential regulator of Elf5 in the context of breast cancer. Understanding the role of DNA methylation in regulating Elf5 in breast cancer suggests that epigenetic regulation is a promising therapeutic target for inhibiting breast cancer metastasis.