Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/40533
Title: The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer.
Authors: Magnani, L
Patten, DK
Nguyen, VTM
Hong, S-P
Steel, JH
Patel, N
Lombardo, Y
Faronato, M
Gomes, AR
Woodley, L
Page, Karen
Guttery, David
Primrose, Lindsay
Fernandez Garcia, D
Shaw, Jacqui
Viola, P
Green, A
Nolan, C
Ellis, IO
Rakha, EA
Shousha, S
Lam, EW-F
Győrffy, B
Lupien, M
Coombes, RC
First Published: 15-Jun-2015
Publisher: Impact Journals
Citation: Oncotarget, 2015, 6 (26), pp. 21878-21891
Abstract: 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.
DOI Link: 10.18632/oncotarget.4243
eISSN: 1949-2553
Links: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=4243&path[]=11612
http://hdl.handle.net/2381/40533
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2015. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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