Introduction/Background Epigenetics, shaping cancer through DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, plays a key role in tumor initiation, progression, and invasion. Extensive clinical data backs the importance of retinoblastoma-binding protein 4 (RBBP4) in various human cancers. Also known as histone-binding protein 4, RBBP4 functions as a nuclear factor, involved in chromatin remodeling and histone assistance within multiple epigenetic complexes—NuRD, PRC2, and SIN3A. Its impact is vital in advancing hepatocellular carcinoma, acute myeloid leukemia, glioblastoma, along with colon, lung, and breast cancers

Methodology We comprehensively reviewed the scientific literature using PubMed and Google Scholar databases to highlight the potential role of RBBP4 in breast cancer (BC) tumorigenesis.

Results Our review underscores epigenetic alterations’ significance in BC tumorigenesis. Among aberrant epigenetic factors associated with BC, RBBP4 seems to be linked to aggressive subtypes like triple negative BC, and exhibits high expression in BC cells. Based on classic BC biomarkers (ER, PR, HER-2), RBBP4 shows a negative correlation with ER and PR, but not with HER-2. High RBBP4 expression indicates poor prognosis, correlating significantly with lymph node metastasis and shorter overall survival. RBBP4 (or RBBP4/RBBP7 via NuRD complex) interacts with co-factors (e.g., HDAC1, BCL11A, SALL4), influencing gene expression and promoting tumorigenesis. Particularly, the interaction of SALL4 and RBBP4 activates the PI3K/AKT pathway, boosting cell proliferation in HER2+ BC models. Additionally, RBBP4’s role in triple-negative BC progression involves regulating epithelial-mesenchymal transition, likely via the Wnt/beta-catenin pathway.

Conclusion RBBP4 (or RBBP4/7) are critical to proliferation of triple-negative BC and maintenance of the cancer stem cell population. Its high expression may constitute an independent biomarker of poor prognosis in BC patients.

Disclosures None