Varışli, LokmanDancik, Garrett M.Tolan, VeyselVlahopoulos, Spiros2023-11-272023-11-2731.10.2023Varışli L., Dancik G.M., Tolan V., Vlahopoulos S. (2023). Critical roles of SRC-3 in the development and progression of breast cancer, rendering it a prospective clinical target. Cancers (Basel). 15(21), 5242. doi: 10.3390/cancers152152422072-6694https://www.mdpi.com/2072-6694/15/21/5242https://hdl.handle.net/11468/13050Breast cancer (BCa) is the most frequently diagnosed malignant tumor in women and is also one of the leading causes of cancer-related death. Most breast tumors are hormone-dependent and estrogen signaling plays a critical role in promoting the survival and malignant behaviors of these cells. Estrogen signaling involves ligand-activated cytoplasmic estrogen receptors that translocate to the nucleus with various co-regulators, such as steroid receptor co-activator (SRC) family members, and bind to the promoters of target genes and regulate their expression. SRC-3 is a member of this family that interacts with, and enhances, the transcriptional activity of the ligand activated estrogen receptor. Although SRC-3 has important roles in normal homeostasis and developmental processes, it has been shown to be amplified and overexpressed in breast cancer and to promote malignancy. The malignancy-promoting potential of SRC-3 is diverse and involves both promoting malignant behavior of tumor cells and creating a tumor microenvironment that has an immunosuppressive phenotype. SRC-3 also inhibits the recruitment of tumor-infiltrating lymphocytes with effector function and promotes stemness. Furthermore, SRC-3 is also involved in the development of resistance to hormone therapy and immunotherapy during breast cancer treatment. The versatility of SRC-3 in promoting breast cancer malignancy in this way makes it a good target, and methodical targeting of SRC-3 probably will be important for the success of breast cancer treatment.eninfo:eu-repo/semantics/openAccessSRC-3Breast cancerEstrogen signalingTumor infiltrating cellsTumor microenvironmentArticle15215242WOS:0011003271000012-s2.0-851766004373795841710.3390/cancers15215242Q1N/A