A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells.
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ICR Authors
Authors
Domenici, G
Aurrekoetxea-Rodríguez, I
Simões, BM
Rábano, M
Lee, SY
Millán, JS
Comaills, V
Oliemuller, E
López-Ruiz, JA
Zabalza, I
Howard, BA
Kypta, RM
Vivanco, MD
Aurrekoetxea-Rodríguez, I
Simões, BM
Rábano, M
Lee, SY
Millán, JS
Comaills, V
Oliemuller, E
López-Ruiz, JA
Zabalza, I
Howard, BA
Kypta, RM
Vivanco, MD
Document Type
Journal Article
Date
2019-04-25
Date Accepted
2018-12-07
Abstract
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.
Citation
Oncogene, 2019, 38 (17), pp. 3151 - 3169
Source Title
Publisher
Springer Science and Business Media LLC
ISSN
0950-9232
eISSN
1476-5594
Collections
Research Team
Endocrine control mechanisms
Molecular Cell Biology
Molecular Cell Biology