Imperial College London

DrLucaMagnani

Faculty of MedicineDepartment of Surgery & Cancer

Principal Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
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Location

 

140ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Faronato:2015:10.18632/oncotarget.4164,
author = {Faronato, M and Nguyen, VTM and Patten, DK and Lombardo, Y and Steel, JH and Patel, N and Woodley, L and Shousha, S and Coombes, RC and Magnani, LM},
doi = {10.18632/oncotarget.4164},
journal = {Oncotarget},
pages = {22467--22479},
title = {DMXL2 drives epithelial to mesenchymal transition in hormonal therapy resistant breast cancer through Notch hyper-activation},
url = {http://dx.doi.org/10.18632/oncotarget.4164},
volume = {6},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The acquisition of endocrine therapy resistance in estrogen receptor α (ERα) breast cancer patients represents a major clinical problem. Notch signalling has been extensively linked to breast cancer especially in patients who fail to respond to endocrine therapy. Following activation, Notch intracellular domain is released and enters the nucleus where activates transcription of target genes. The numerous steps that cascade after activation of the receptor complicate using Notch as biomarker. Hence, this warrants the development of reliable indicators of Notch activity. DMXL2 is a novel regulator of Notch signalling not yet investigated in breast cancer. Here, we demonstrate that DMXL2 is overexpressed in a subset of endocrine therapy resistant breast cancer cell lines where it promotes epithelial to mesenchymal transition through hyper-activation of Notch signalling via V-ATPase dependent acidification. Following DMXL2 depletion or treatment with Bafilomycin A1, both EMT targets and Notch signalling pathway significantly decrease. We show for the first time that DMXL2 protein levels are significantly increased in ERα positive breast cancer patients that progress after endocrine therapy. Finally, we demonstrate that DMXL2 is a transmembrane protein with a potential extra-cellular domain. These findings identify DMXL2 as a novel, functional biomarker for ERα positive breast cancer.
AU - Faronato,M
AU - Nguyen,VTM
AU - Patten,DK
AU - Lombardo,Y
AU - Steel,JH
AU - Patel,N
AU - Woodley,L
AU - Shousha,S
AU - Coombes,RC
AU - Magnani,LM
DO - 10.18632/oncotarget.4164
EP - 22479
PY - 2015///
SN - 1949-2553
SP - 22467
TI - DMXL2 drives epithelial to mesenchymal transition in hormonal therapy resistant breast cancer through Notch hyper-activation
T2 - Oncotarget
UR - http://dx.doi.org/10.18632/oncotarget.4164
UR - http://hdl.handle.net/10044/1/23241
VL - 6
ER -