The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
WT1 Mutants Reveal SRPK1 to Be a Downstream Angiogenesis Target by Altering VEGF Splicing
Open accessAbstract
Summary Angiogenesis is regulated by the balance of pro-angiogenic VEGF165 and anti-angiogenic VEGF165b splice isoforms. Mutations in WT1, the Wilms’ tumour suppressor gene, suppress VEGF165b and cause abnormal gonadogenesis, renal failure and Wilms’ tumours. In WT1 mutant cells, reduced VEGF165b was due to lack of WT1 mediated transcriptional repression of the splicing factor kinase SRPK1. WT1 bound to the SRPK1 promoter, and repressed expression through a specific WT1 binding-site. In WT1 mutant cells SRPK1-mediated hyperphosphorylation of the oncogenic RNA binding protein SRSF1 regulated splicing of VEGF, and rendered WT1 mutant cells pro-angiogenic. Altered VEGF splicing was reversed by wildtype WT1, knockdown of SRSF1 or SRPK1 and inhibition of SRPK1, which prevented in vitro and in vivo angiogenesis and associated tumour growth.
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Self-citationVEGF165b, an Inhibitory Vascular Endothelial Growth Factor Splice Variant
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Cited by
Alternative splicing: a pivotal step between eukaryotic transcription and translation
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RNA splicing factors as oncoproteins and tumour suppressors
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Hallmarks of alternative splicing in cancer
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Metadata
- Authors
- Amin, E. M., Oltean, S., Hua, J., Gammons, M. V. R., Hamdollah-Zadeh, M., Welsh, G. I., Cheung, M.-K., Ni, L., Kase, S., Rennel, E. S., Symonds, K. E., Nowak, D. G., Royer-Pokora, B., Saleem, M. A., Hagiwara, M., Schumacher, V. A., Harper, S. J., Hinton, D. R., Bates, D. O., & Ladomery, M. R.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 20
- Issue
- 6
- Pages
- 768-780
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2027701384
- Cited by
- 253
- References
- 43
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Amin, E. M., Oltean, S., Hua, J., Gammons, M. V. R., Hamdollah-Zadeh, M., Welsh, G. I., Cheung, M.-K., Ni, L., Kase, S., Rennel, E. S., Symonds, K. E., Nowak, D. G., Royer-Pokora, B., Saleem, M. A., Hagiwara, M., Schumacher, V. A., Harper, S. J., Hinton, D. R., Bates, D. O., & Ladomery, M. R. (2011). WT1 Mutants Reveal SRPK1 to Be a Downstream Angiogenesis Target by Altering VEGF Splicing. Cancer Cell. https://doi.org/10.1016/j.ccr.2011.10.016
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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