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Global transcriptional analysis identifies a novel role for SOX4 in 2 tumor-induced angiogenesis

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Title: Global transcriptional analysis identifies a novel role for SOX4 in 2 tumor-induced angiogenesis
Authors: Vervoort, SJ
De Jong, OG
Roukens, MG
Frederiks, CL
Vermeulen, JF
Lourenço, AR
Bella, L
Vidakovic, AT
Sandoval, JL
Moelans, C
Van Amersfoort, M
Dallman, MJ
Bruna, A
Caldas, C
Nieuwenhuis, E
Van der Wall, E
Derksen, P
Van Diest, P
Verhaar, MC
Lam, EW-F
Mokry, M
Coffer, PJ
Item Type: Journal Article
Abstract: The expression of the transcription factor SOX4 is increased in many human cancers, however, the pro-oncogenic capacity of SOX4 can vary greatly depending on the type of tumor. Both the contextual nature and the mechanisms underlying the pro-oncogenic SOX4 response remain unexplored. Here, we demonstrate that in mammary tumorigenesis, the SOX4 transcriptional network is dictated by the epigenome and is enriched for pro-angiogenic processes. We show that SOX4 directly regulates endothelin-1 (ET-1) expression and can thereby promote tumor-induced angiogenesis both in vitro and in vivo. Furthermore, in breast tumors, SOX4 expression correlates with blood vessel density and size, and predicts poor-prognosis in patients with breast cancer. Our data provide novel mechanistic insights into context-dependent SOX4 target gene selection, and uncover a novel pro-oncogenic role for this transcription factor in promoting tumor-induced angiogenesis. These findings establish a key role for SOX4 in promoting metastasis through exploiting diverse pro-tumorigenic pathways.
Issue Date: 3-Dec-2018
Date of Acceptance: 7-Nov-2018
URI: http://hdl.handle.net/10044/1/66286
DOI: https://dx.doi.org/10.7554/eLife.27706
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd
Journal / Book Title: eLife
Volume: 7
Copyright Statement: Copyright © 2018 Vervoort et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Sponsor/Funder: Cancer Research UK
Breast Cancer Now
Breast Cancer Now
Medical Research Council (MRC)
Funder's Grant Number: C37/A12011
2012NovemberPhD016
2012MayPR070
MR/N012097/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
EPITHELIAL-MESENCHYMAL TRANSITION
BREAST-CANCER METASTASIS
ENDOTHELIN-B-RECEPTOR
PROSTATE-CANCER
CLAUDIN-LOW
EXPRESSION
GENE
CELLS
REGULATORS
REVEALS
Angiogenesis
EDN1
Endothelin-1
SOX4
breast cancer
cancer biology
cell biology
human
mouse
tumor biology
zebrafish
Publication Status: Published
Article Number: e27706
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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