ZFIN ID: ZDB-PUB-181206-1
Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis
Vervoort, S.J., de Jong, O.G., Roukens, M.G., Frederiks, C.L., Vermeulen, J.F., Lourenço, A.R., Bella, L., Vidakovic, A.T., Sandoval, J.L., Moelans, C., van Amersfoort, M., Dallman, M.J., Bruna, A., Caldas, C., Nieuwenhuis, E., van der Wall, E., Derksen, P., van Diest, P., Verhaar, M.C., Lam, E.W., Mokry, M., Coffer, P.J.
Date: 2018
Source: eLIFE   7: (Journal)
Registered Authors: Dallman, Maggie
Keywords: Angiogenesis, EDN1, Endothelin-1, SOX4, breast cancer, cancer biology, cell biology, human, mouse, tumor biology, zebrafish
MeSH Terms:
  • Animals
  • Breast Neoplasms/blood supply*
  • Breast Neoplasms/genetics*
  • Breast Neoplasms/pathology
  • Chromatin/metabolism
  • Culture Media, Conditioned/pharmacology
  • Endothelin-1/metabolism
  • Epigenesis, Genetic
  • Epithelial Cells/drug effects
  • Epithelial Cells/metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic/drug effects
  • Gene Regulatory Networks
  • HEK293 Cells
  • Humans
  • Neoplasm Metastasis
  • Neovascularization, Pathologic/genetics*
  • Promoter Regions, Genetic/genetics
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • SOXC Transcription Factors/genetics
  • SOXC Transcription Factors/metabolism*
  • Survival Analysis
  • Trans-Activators/metabolism
  • Transcription, Genetic*
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed: 30507376 Full text @ Elife
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.