TY - JOUR
T1 - Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis
AU - Vervoort, Stephin J.
AU - de Jong, Olivier G.
AU - Guy Roukens, M.
AU - Frederiks, Cynthia L.
AU - Vermeulen, Jeroen F.
AU - Lourenço, Ana Rita
AU - Bella, Laura
AU - Vidakovic, Ana Tufegdzic
AU - Sandoval, José L.
AU - Moelans, Cathy
AU - van Amersfoort, Miranda
AU - Dallman, Margaret J.
AU - Bruna, Alejandra
AU - Caldas, Carlos
AU - Nieuwenhuis, Edward
AU - van der Wall, Elsken
AU - Derksen, Patrick
AU - van Diest, Paul
AU - Verhaar, Marianne C.
AU - Lam, Eric W.F.
AU - Mokry, Michal
AU - Coffer, Paul J.
N1 - Publisher Copyright:
© Vervoort et al.
PY - 2018/12/3
Y1 - 2018/12/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061194063&partnerID=8YFLogxK
U2 - 10.7554/eLife.27706
DO - 10.7554/eLife.27706
M3 - Article
C2 - 30507376
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e27706
ER -