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Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target

Journal

CANCERS
Volume 15, Issue 21, Pages -

Publisher

MDPI
DOI: 10.3390/cancers15215242

Keywords

breast cancer; SRC-3; estrogen signaling; tumor microenvironment; tumor infiltrating cells

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Breast cancer is one of the most commonly diagnosed malignancies in women, and estrogen signaling plays a critical role in its development and progression. SRC-3 is an important factor in breast cancer and has versatile effects in promoting malignant behavior of tumor cells and creating an immunosuppressive tumor microenvironment.
Simple Summary Breast cancer is one of the most commonly diagnosed malignancies in women and is also a leading cause of cancer related death. Estrogens play crucial roles in the development and progression of breast cancer, and estrogen signaling is generally mediated by estrogen receptors. Steroid receptor co-activator protein family members are transcriptional activators that interact with steroid receptors, including estrogen receptors. SRC-3 is a member of this family and has been shown to be overexpressed and/or amplified in breast cancer. Here, we review and discuss the versatile effects of SRC-3 in breast malignancy and its potential as a therapeutic target.Abstract Breast 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.

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