Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis
| Autor: | 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 |
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| Přispěvatelé: | Bruna, Alejandra [0000-0003-1214-9665], Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
Transcription
Genetic QH301-705.5 Science Breast Neoplasms Epigenesis Genetic SOXC Transcription Factors breast cancer cell biology Animals Humans Gene Regulatory Networks RNA Messenger human Biology (General) Neoplasm Metastasis Promoter Regions Genetic mouse cancer biology tumor biology Neovascularization Pathologic Endothelin-1 Gene Expression Profiling Epithelial Cells zebrafish Survival Analysis Xenograft Model Antitumor Assays Chromatin Gene Expression Regulation Neoplastic HEK293 Cells Culture Media Conditioned Trans-Activators Medicine Female EDN1 SOX4 Angiogenesis Research Article |
| Zdroj: | eLife, 7. eLife Sciences Publications eLife eLife, Vol 7 (2018) |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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