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

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. Estroge...

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Bibliographic Details
Published in:Cancers 2023-11, Vol.15 (21), p.5242
Main Authors: Varisli, Lokman, Dancik, Garrett M, Tolan, Veysel, Vlahopoulos, Spiros
Format: Article
Language:English
Subjects:
Breast cancer
Cancer therapies
Cytoplasm
Development and progression
Diagnosis
Estrogen
Estrogen receptors
Estrogens
Homeostasis
Immunotherapy
Lymphocytes
Malignancy
Medical prognosis
Metastasis
Pathogenesis
Phenotypes
Proteins
Src protein
Steroid hormone receptors
Steroids
Therapeutic targets
Transcription factors
Tumor cells
Tumor microenvironment
Tumor-infiltrating lymphocytes
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15215242