ArticleBreast cancer research : BCR2022
Steroid receptor coactivator-3 inhibition generates breast cancer antitumor immune microenvironment.
Article in Breast cancer research : BCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Steroid receptor coactivator 3-deficient regulatory T cells eradicate multiple solid tumors in syngeneic mouse models.Oncoimmunology · 2026Article
- LSD1 Promotes Immune Exclusion and Suppresses IFN-γ-Associated Transcriptional Programs in Triple-Negative Breast Cancer.Cancers · 2026Article
- Steroid receptor coactivators: from basic research to translational opportunities.Endocrine reviews · 2026Review
- Steroid receptor coactivators in immunity - From function to emerging translational opportunities.The Journal of biological chemistry · 2026Review
- The USP1-WDR48 deubiquitinase complex functions as a molecular switch regulating tumor-associated macrophage activation and anti-tumor response.Cell death and differentiation · 2026Article
- Targeting steroid receptor coactivators for the treatment of benign female reproductive disorders.Endocrine connections · 2025Review
- A long journey to the discovery of nuclear receptor coactivator existence, physiology, pathology, and therapy.The Journal of biological chemistry · 2025Article
- Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.International journal of biological sciences · 2025Review
- NCOA3 knockdown delays human embryo development.Heliyon · 2024Article
- Knockdown of SCN5A alters metabolic-associated genes and aggravates hypertrophy in the cardiomyoblast.Molecular biology reports · 2024Article
- Function of Steroid Receptor Coactivators in T Cells and Cancers: Implications for Cancer Immunotherapy.Critical reviews in immunology · 2024Review
- Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma.PloS one · 2024Article
- Steroid receptor coactivators in Treg and Th17 cell biology and function.Frontiers in immunology · 2024Review
- Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.Cancers · 2023Review
- Steroid receptor coactivator 3 is a key modulator of regulatory T cell-mediated tumor evasion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Steroid receptor coactivators - their role in immunity.Frontiers in immunology · 2022Review
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5 authors at 1 institution in 1 country.
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Abstract
backgroundThe tumor immune microenvironment (TIME) generated by cancer-infiltrating immune cells has a crucial role in promoting or suppressing breast cancer progression. However, whether the steroid receptor coactivator-3 (SRC-3) modulates TIME to progress breast cancer is unclear. Therefore, the present study evaluates whether SRC-3 generates a tumor-promoting TIME in breast tumors using a syngeneic immune-intact mouse model of breast cancer.
methodsWe employed E0771 and 4T1 breast cancer in immune-intact syngeneic female C57BL/6 and BALB/c mice, respectively. SI-2, a specific small-molecule inhibitor of SRC-3, was administered daily (2.5 mg/kg) to E0771 and 4T1 breast tumor-bearing immune-intact mice. In addition, SRC-3 knockdown (KD)-E0771 and SRC-3 KD-4T1 cells and their parental breast cancer cells were injected into their syngeneic immune-intact female mice versus immune-deficiency mice to validate that the host immune system is required for breast tumor suppression by SRC-3 KD in immune-intact mice. Furthermore, tumor-infiltrating immune cells (such as CD4+, CD8+, CD56+, and Foxp3+ cells) in E0771 and 4T1 breast cancers treated with SI-2 and in SRC-3 KD E0771 and 4T1 breast cancers were determined by immunohistochemistry. Additionally, cytokine levels in SI-2-treated and SRC-3 KD E0771 breast tumors and their control cancers were defined with a Mouse Cytokine Array.
resultsSRC-3 inhibition by SI-2 significantly suppressed the progression of breast cancer cells (E0771 and 4T1) into breast cancers in immune-intact syngeneic female mice. SRC-3 KD-E0771 and -4T1 breast cancer cells did not produce well-developed tumors in immune-intact syngeneic female mice compared to their parental cells, but SRC-3 KD breast cancers were well developed in immune-defective host mice. SRC-3 inhibition by SI-2 and SRC-3 KD effectively increased the numbers of cytotoxic immune cells, such as CD4+ and CD8+ T cells and CD56+ NK cells, and Interferon γ (Ifng) in breast cancers compared to vehicle. However, SI-2 treatment reduced the number of tumor-infiltrating CD4+/Foxp3+ regulatory T (Treg) cells compared to vehicle treatment. In addition, SRC-3 inhibition by SI-2 and SRC-3 KD increased C-X-C motif chemokine ligand 9 (Cxcl9) expression in breast cancer to recruit C-X-C motif chemokine receptor 3 (Cxcr3)-expressing cytotoxic immune cells into breast tumors.
conclusionsSRC-3 is a critical immunomodulator in breast cancer, generating a protumor immune microenvironment. SRC-3 inhibition by SI-2 or SRC-3 KD activates the Cxcl9/Cxcr3 axis in breast tumors and enhances the antitumor immune microenvironment to suppress breast cancer progression.
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