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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10648290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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