A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells.
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Date
2019-04-25ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Breast
Cell Line
Epithelial Cells
Humans
Breast Neoplasms
Tamoxifen
Estrogens
Signal Transduction
Cell Proliferation
Gene Expression Regulation, Neoplastic
Up-Regulation
Drug Resistance, Neoplasm
Female
Neoplastic Stem Cells
SOXB1 Transcription Factors
SOX9 Transcription Factor
MCF-7 Cells
Research team
Endocrine control mechanisms
Molecular Cell Biology
Language
eng
Date accepted
2018-12-07
License start date
2019-04
Citation
Oncogene, 2019, 38 (17), pp. 3151 - 3169
Publisher
Springer Science and Business Media LLC