A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells.

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

Oncogene

journal_title

Oncogene

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

doi

10.1038/s41388-018-0656-7

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

3151-3169

issue

17

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-018-0656-7

journal_volume

38

pub_type

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