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A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells
Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and los...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756022/ https://www.ncbi.nlm.nih.gov/pubmed/30622340 http://dx.doi.org/10.1038/s41388-018-0656-7 |
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author | Domenici, Giacomo Aurrekoetxea-Rodríguez, Iskander Simões, Bruno M. Rábano, Miriam Lee, So Young Millán, Julia San Comaills, Valentine Oliemuller, Erik López-Ruiz, José A. Zabalza, Ignacio Howard, Beatrice A. Kypta, Robert M. Vivanco, Maria dM |
author_facet | Domenici, Giacomo Aurrekoetxea-Rodríguez, Iskander Simões, Bruno M. Rábano, Miriam Lee, So Young Millán, Julia San Comaills, Valentine Oliemuller, Erik López-Ruiz, José A. Zabalza, Ignacio Howard, Beatrice A. Kypta, Robert M. Vivanco, Maria dM |
author_sort | Domenici, Giacomo |
collection | PubMed |
description | Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assays indicate that Sox9 is implicated in the maintenance of human breast luminal progenitor cells. CRISPR/Cas knockout of Sox9 reduces growth of tamoxifen-resistant breast tumours in vivo. Mechanistically, Sox9 acts downstream of Sox2 to control luminal progenitor cell content and is required for expression of the cancer stem cell marker ALDH1A3 and Wnt signalling activity. Sox9 is elevated in breast cancer patients after endocrine therapy failure. This new regulatory axis highlights the relevance of SOX family transcription factors as potential therapeutic targets in breast cancer. |
format | Online Article Text |
id | pubmed-6756022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67560222019-09-24 A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells Domenici, Giacomo Aurrekoetxea-Rodríguez, Iskander Simões, Bruno M. Rábano, Miriam Lee, So Young Millán, Julia San Comaills, Valentine Oliemuller, Erik López-Ruiz, José A. Zabalza, Ignacio Howard, Beatrice A. Kypta, Robert M. Vivanco, Maria dM Oncogene Article Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assays indicate that Sox9 is implicated in the maintenance of human breast luminal progenitor cells. CRISPR/Cas knockout of Sox9 reduces growth of tamoxifen-resistant breast tumours in vivo. Mechanistically, Sox9 acts downstream of Sox2 to control luminal progenitor cell content and is required for expression of the cancer stem cell marker ALDH1A3 and Wnt signalling activity. Sox9 is elevated in breast cancer patients after endocrine therapy failure. This new regulatory axis highlights the relevance of SOX family transcription factors as potential therapeutic targets in breast cancer. Nature Publishing Group UK 2019-01-08 2019 /pmc/articles/PMC6756022/ /pubmed/30622340 http://dx.doi.org/10.1038/s41388-018-0656-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Domenici, Giacomo Aurrekoetxea-Rodríguez, Iskander Simões, Bruno M. Rábano, Miriam Lee, So Young Millán, Julia San Comaills, Valentine Oliemuller, Erik López-Ruiz, José A. Zabalza, Ignacio Howard, Beatrice A. Kypta, Robert M. Vivanco, Maria dM A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells |
title | A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells |
title_full | A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells |
title_fullStr | A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells |
title_full_unstemmed | A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells |
title_short | A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells |
title_sort | sox2–sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756022/ https://www.ncbi.nlm.nih.gov/pubmed/30622340 http://dx.doi.org/10.1038/s41388-018-0656-7 |
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