Journal
ONCOGENE
Volume 38, Issue 17, Pages 3151-3169Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41388-018-0656-7
Keywords
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Funding
- Spanish Ministry of Education and Science
- Institute of Health Carlos III [PI14/01328]
- Department of Education of the Government of the Autonomous Community of the Basque Country [PRE_2013_1_991]
- Department of Health of the Government of the Autonomous Community of the Basque Country [2014111145]
- Department of Industry, Tourism and Trade (Etortek) of the Government of the Autonomous Community of the Basque Country
- Department of Innovation Technology of the Government of the Autonomous Community of the Basque Country
- RED Nurcamein
- Breast Cancer Now
- [SAF2017-84934-R]
- [SAF2017-84092-R]
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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.
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