Imperial College London
Portrait Picture

DrLeandroCastellano

Faculty of Medicine, Department of Surgery & Cancer

Visiting Reader
 
 
 
//

Contact

 

+44 (0)20 7594 2822l.castellano Website

 
 
//

Location

 

ICTEM buildingHammersmith Campus

//

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},
pages = {1--15},
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}
}
Download

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
EP  - 15
PY  - 2015///
SN  - 2041-1723
SP  - 1
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  - https://www.nature.com/articles/ncomms10044
UR  - http://hdl.handle.net/10044/1/33830
VL  - 6
ER  -
Download