PUBLICATION
Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis
- Authors
- 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.
- ID
- ZDB-PUB-181206-1
- 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
-
- Gene Expression Profiling
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Humans
- Gene Regulatory Networks
- Endothelin-1/metabolism
- Epithelial Cells/drug effects
- Epithelial Cells/metabolism
- Trans-Activators/metabolism
- Neovascularization, Pathologic/genetics*
- SOXC Transcription Factors/genetics
- SOXC Transcription Factors/metabolism*
- Female
- Culture Media, Conditioned/pharmacology
- Transcription, Genetic*
- Chromatin/metabolism
- Animals
- Gene Expression Regulation, Neoplastic/drug effects
- Survival Analysis
- Epigenesis, Genetic
- HEK293 Cells
- Promoter Regions, Genetic/genetics
- Breast Neoplasms/blood supply*
- Breast Neoplasms/genetics*
- Breast Neoplasms/pathology
- Xenograft Model Antitumor Assays
- Neoplasm Metastasis
- Zebrafish
- PubMed
- 30507376 Full text @ Elife
Citation
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. (2018) Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis. eLIFE. 7:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping