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.
journal_name
Oncogenejournal_title
Oncogeneauthors
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 MDdoi
10.1038/s41388-018-0656-7subject
Has Abstractpub_date
2019-04-01 00:00:00pages
3151-3169issue
17eissn
0950-9232issn
1476-5594pii
10.1038/s41388-018-0656-7journal_volume
38pub_type
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