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{Piva:2014:10.1002/emmm.201303411,
author = {Piva, M and Domenici, G and Iriondo, O and Rábano, M and Simões, BM and Comaills, V and Barredo, I and López-Ruiz, JA and Zabalza, I and Kypta, R and Vivanco, MD},
doi = {10.1002/emmm.201303411},
journal = {EMBO Molecular Medicine},
pages = {66--79},
title = {Sox2 promotes tamoxifen resistance in breast cancer cells},
url = {http://dx.doi.org/10.1002/emmm.201303411},
volume = {6},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Development of resistance to therapy continues to be a serious clinical problem in breast cancer management. Cancer stem/progenitor cells have been shown to play roles in resistance to chemo- and radiotherapy. Here, we examined their role in the development of resistance to the oestrogen receptor antagonist tamoxifen. Tamoxifen-resistant cells were enriched for stem/progenitors and expressed high levels of the stem cell marker Sox2. Silencing of the SOX2 gene reduced the size of the stem/progenitor cell population and restored sensitivity to tamoxifen. Conversely, ectopic expression of Sox2 reduced tamoxifen sensitivity in vitro and in vivo. Gene expression profiling revealed activation of the Wnt signalling pathway in Sox2-expressing cells, and inhibition of Wnt signalling sensitized resistant cells to tamoxifen. Examination of patient tumours indicated that Sox2 levels are higher in patients after endocrine therapy failure, and also in the primary tumours of these patients, compared to those of responders. Together, these results suggest that development of tamoxifen resistance is driven by Sox2-dependent activation of Wnt signalling in cancer stem/progenitor cells.
AU  - Piva,M
AU  - Domenici,G
AU  - Iriondo,O
AU  - Rábano,M
AU  - Simões,BM
AU  - Comaills,V
AU  - Barredo,I
AU  - López-Ruiz,JA
AU  - Zabalza,I
AU  - Kypta,R
AU  - Vivanco,MD
DO  - 10.1002/emmm.201303411
EP  - 79
PY  - 2014///
SN  - 1757-4676
SP  - 66
TI  - Sox2 promotes tamoxifen resistance in breast cancer cells
T2  - EMBO Molecular Medicine
UR  - http://dx.doi.org/10.1002/emmm.201303411
UR  - https://www.embopress.org/doi/full/10.1002/emmm.201303411
UR  - http://hdl.handle.net/10044/1/18473
VL  - 6
ER  -
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