Epigenetic Signatures of Breast Cancer Metastasis: Deep Insights into HDACs, SIRT1 and Long Non-Coding RNAs

Breast cancer (BC) remains the most common malignancy among women, with metastasis occur-ring in roughly 20–30% of patients and accounting for most BC-related deaths. While genetic mutations are central to tumorigenesis, they cannot fully explain the metastatic capacity of cancer cells. Increasing attention has therefore turned to epigenetic regulation, particularly the role of long noncoding RNAs (lncRNAs), which control gene activity without altering DNA sequences. Yet, most current knowledge of epigenetic alterations is derived from studies of early cancer development, and the events that specifically promote metastasis remain less well defined. This review addresses that gap by outlining major epigenetic mechanisms implicated in BC progression. Our focus in particular is initially devoted to driver epigenetic events including DNA methylation, histone modifications, we highlight, in depth, the functional significance of histone deacetylases (HDACs) particularly the dual role of sirtuin1 (SIRT1) in BC metastasis. Finally, we offer an in-depth overview of the of the various potential functions and mechanisms for lncRNAs as a second epigenetic regulator affecting BC cell invasiveness and metastasis.