학술논문
Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis
Document Type
Report
Author
Vervoort, Stephin J; de Jong, Olivier G; Roukens, M Guy; Frederiks, Cynthia L; Vermeulen, Jeroen F; Lourenço, Ana Rita; Bella, Laura; Vidakovic, Ana Tufegdzic; Sandoval, José L; Moelans, Cathy; van Amersfoort, Miranda; Dallman, Margaret J; Bruna, Alejandra; Caldas, Carlos; Nieuwenhuis, Edward; van der Wall, Elsken; Derksen, Patrick; van Diest, Paul; Verhaar, Marianne C; Lam, Eric W-F; Mokry, Michal; Coffer, Paul J
Source
eLife. December 3, 2018, Vol. 7
Subject
Language
English
ISSN
2050-084X
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.
Byline: Stephin J Vervoort, Olivier G de Jong, M Guy Roukens, Cynthia L Frederiks, Jeroen F Vermeulen, Ana Rita Lourenço, Laura Bella, Ana Tufegdzic Vidakovic, José L Sandoval, Cathy Moelans, [...]
Byline: Stephin J Vervoort, Olivier G de Jong, M Guy Roukens, Cynthia L Frederiks, Jeroen F Vermeulen, Ana Rita Lourenço, Laura Bella, Ana Tufegdzic Vidakovic, José L Sandoval, Cathy Moelans, [...]