Imperial College London
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DrRobertKypta

Faculty of Medicine, Department of Surgery & Cancer

Senior Lecturer in Cancer Biology
 
 
 
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Contact

 

r.kypta Website

 
 
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Location

 

4007Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Domenici:2019:10.1038/s41388-018-0656-7,
author = {Domenici, G and Aurrekoetxea-Rodríguez, I and Simões, BM and Rábano, M and Lee, SY and Millán, JS and Comaills, V and Oliemuller, E and López-Ruiz, JA and Zabalza, I and Howard, BA and Kypta, RM and Vivanco, MD},
doi = {10.1038/s41388-018-0656-7},
journal = {Oncogene},
pages = {3151--3169},
title = {A Sox2–Sox9 signalling axis maintains human breast luminalprogenitor and breast cancer stem cells},
url = {http://dx.doi.org/10.1038/s41388-018-0656-7},
volume = {38},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Domenici,G
AU  - Aurrekoetxea-Rodríguez,I
AU  - Simões,BM
AU  - Rábano,M
AU  - Lee,SY
AU  - Millán,JS
AU  - Comaills,V
AU  - Oliemuller,E
AU  - López-Ruiz,JA
AU  - Zabalza,I
AU  - Howard,BA
AU  - Kypta,RM
AU  - Vivanco,MD
DO  - 10.1038/s41388-018-0656-7
EP  - 3169
PY  - 2019///
SN  - 0950-9232
SP  - 3151
TI  - A Sox2–Sox9 signalling axis maintains human breast luminalprogenitor and breast cancer stem cells
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/s41388-018-0656-7
UR  - http://hdl.handle.net/10044/1/66983
VL  - 38
ER  -
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