Imperial College London

ProfessorSimakAli

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Molecular Endocrine Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2811simak.ali

 
 
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Location

 

133ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Nguyen:2015:10.1038/ncomms10044,
author = {Nguyen, VTM and Barozzi, I and Faronato, M and Lombardo, Y and Steel, JH and Patel, N and Darbre, P and Castellano, L and Gyorffy, B and Woodley, L and Meira, A and Patten, DL and Vircillo, V and Periyasamy, M and Ali, S and Frige, G and Minucci, S and Coombes, RC and Magnani, L},
doi = {10.1038/ncomms10044},
journal = {Nature Communications},
title = {Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion},
url = {http://dx.doi.org/10.1038/ncomms10044},
volume = {6},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Endocrine therapies target the activation of the oestrogen receptor alpha (ERa) via distinctmechanisms, but it is not clear whether breast cancer cells can adapt to treatment usingdrug-specific mechanisms. Here we demonstrate that resistance emerges via drug-specificepigenetic reprogramming. Resistant cells display a spectrum of phenotypical changes withinvasive phenotypes evolving in lines resistant to the aromatase inhibitor (AI). Orthogonalgenomics analysis of reprogrammed regulatory regions identifies individual drug-inducedepigenetic states involving large topologically associating domains (TADs) and the activationof super-enhancers. AI-resistant cells activate endogenous cholesterol biosynthesis (CB)through stable epigenetic activation in vitro and in vivo. Mechanistically, CB sparks theconstitutive activation of oestrogen receptors alpha (ERa) in AI-resistant cells, partly via thebiosynthesis of 27-hydroxycholesterol. By targeting CB using statins, ERa binding is reducedand cell invasion is prevented. Epigenomic-led stratification can predict resistance to AI in asubset of ERa-positive patients.
AU - Nguyen,VTM
AU - Barozzi,I
AU - Faronato,M
AU - Lombardo,Y
AU - Steel,JH
AU - Patel,N
AU - Darbre,P
AU - Castellano,L
AU - Gyorffy,B
AU - Woodley,L
AU - Meira,A
AU - Patten,DL
AU - Vircillo,V
AU - Periyasamy,M
AU - Ali,S
AU - Frige,G
AU - Minucci,S
AU - Coombes,RC
AU - Magnani,L
DO - 10.1038/ncomms10044
PY - 2015///
SN - 2041-1723
TI - Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/ncomms10044
UR - http://hdl.handle.net/10044/1/33830
VL - 6
ER -