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

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...

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Autores principales: Varisli, Lokman, Dancik, Garrett M., Tolan, Veysel, Vlahopoulos, Spiros
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648290/
https://www.ncbi.nlm.nih.gov/pubmed/37958417
http://dx.doi.org/10.3390/cancers15215242
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author Varisli, Lokman
Dancik, Garrett M.
Tolan, Veysel
Vlahopoulos, Spiros
author_facet Varisli, Lokman
Dancik, Garrett M.
Tolan, Veysel
Vlahopoulos, Spiros
author_sort Varisli, Lokman
collection PubMed
description 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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spelling pubmed-106482902023-10-31 Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target Varisli, Lokman Dancik, Garrett M. Tolan, Veysel Vlahopoulos, Spiros Cancers (Basel) Review 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. MDPI 2023-10-31 /pmc/articles/PMC10648290/ /pubmed/37958417 http://dx.doi.org/10.3390/cancers15215242 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Varisli, Lokman
Dancik, Garrett M.
Tolan, Veysel
Vlahopoulos, Spiros
Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target
title Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target
title_full Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target
title_fullStr Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target
title_full_unstemmed Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target
title_short Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target
title_sort critical roles of src-3 in the development and progression of breast cancer, rendering it a prospective clinical target
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648290/
https://www.ncbi.nlm.nih.gov/pubmed/37958417
http://dx.doi.org/10.3390/cancers15215242
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