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{Magnani:2015:10.18632/oncotarget.4243,
author = {Magnani, L and Patten, DK and Nguyen, VTM and Hong, SP and Steel, JH and Patel, N and Lombardo, Y and Faronato, M and Gomes, AR and Woodley, L and Page, K and Guttery, D and Primrose, L and Fernandez, Garcia D and Shaw, J and Viola, P and Green, A and Nolan, C and Ellis, IO and Rakha, EA and Shousha, S and Lam, EWF and Gyorffy, B and Lupien, M and Coombes, RC},
doi = {10.18632/oncotarget.4243},
journal = {Oncotarget},
pages = {21878--24891},
title = {The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer.},
url = {http://dx.doi.org/10.18632/oncotarget.4243},
volume = {6},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer.
AU - Magnani,L
AU - Patten,DK
AU - Nguyen,VTM
AU - Hong,SP
AU - Steel,JH
AU - Patel,N
AU - Lombardo,Y
AU - Faronato,M
AU - Gomes,AR
AU - Woodley,L
AU - Page,K
AU - Guttery,D
AU - Primrose,L
AU - Fernandez,Garcia D
AU - Shaw,J
AU - Viola,P
AU - Green,A
AU - Nolan,C
AU - Ellis,IO
AU - Rakha,EA
AU - Shousha,S
AU - Lam,EWF
AU - Gyorffy,B
AU - Lupien,M
AU - Coombes,RC
DO - 10.18632/oncotarget.4243
EP - 24891
PY - 2015///
SN - 1949-2553
SP - 21878
TI - The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer.
T2 - Oncotarget
UR - http://dx.doi.org/10.18632/oncotarget.4243
UR - http://hdl.handle.net/10044/1/23291
VL - 6
ER -