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A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells
The splice variant sVEGFR1-i13 is a truncated version of the cell membrane-spanning VEGFR1 receptor that is devoid of its transmembrane and tyrosine kinase domains. We recently showed the contribution of sVEGFR1-i13 to the progression and the response of squamous lung carcinoma to anti-angiogenic th...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344584/ https://www.ncbi.nlm.nih.gov/pubmed/30674935 http://dx.doi.org/10.1038/s41598-018-36728-y |
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author | Abou Faycal, Cherine Gazzeri, Sylvie Eymin, Beatrice |
author_facet | Abou Faycal, Cherine Gazzeri, Sylvie Eymin, Beatrice |
author_sort | Abou Faycal, Cherine |
collection | PubMed |
description | The splice variant sVEGFR1-i13 is a truncated version of the cell membrane-spanning VEGFR1 receptor that is devoid of its transmembrane and tyrosine kinase domains. We recently showed the contribution of sVEGFR1-i13 to the progression and the response of squamous lung carcinoma to anti-angiogenic therapies. In this study, we identify VEGF165, a splice variant of VEGF-A, as a regulator of sVEGFR1-i13 expression in these tumors, and further show that VEGF(165) cooperates with the transcription factor SOX2 and the splicing factor SRSF2 to control sVEGFR1-i13 expression. We also demonstrate that anti-angiogenic therapies up-regulate sVEGFR1-i13 protein level in squamous lung carcinoma cells by a mechanism involving the VEGF(165)/SOX2/SRSF2 network. Collectively, our results identify for the first time a signaling network that controls VEGFR1 pre-mRNA alternative splicing in cancer cells. |
format | Online Article Text |
id | pubmed-6344584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63445842019-01-28 A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells Abou Faycal, Cherine Gazzeri, Sylvie Eymin, Beatrice Sci Rep Article The splice variant sVEGFR1-i13 is a truncated version of the cell membrane-spanning VEGFR1 receptor that is devoid of its transmembrane and tyrosine kinase domains. We recently showed the contribution of sVEGFR1-i13 to the progression and the response of squamous lung carcinoma to anti-angiogenic therapies. In this study, we identify VEGF165, a splice variant of VEGF-A, as a regulator of sVEGFR1-i13 expression in these tumors, and further show that VEGF(165) cooperates with the transcription factor SOX2 and the splicing factor SRSF2 to control sVEGFR1-i13 expression. We also demonstrate that anti-angiogenic therapies up-regulate sVEGFR1-i13 protein level in squamous lung carcinoma cells by a mechanism involving the VEGF(165)/SOX2/SRSF2 network. Collectively, our results identify for the first time a signaling network that controls VEGFR1 pre-mRNA alternative splicing in cancer cells. Nature Publishing Group UK 2019-01-23 /pmc/articles/PMC6344584/ /pubmed/30674935 http://dx.doi.org/10.1038/s41598-018-36728-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Abou Faycal, Cherine Gazzeri, Sylvie Eymin, Beatrice A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells |
title | A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells |
title_full | A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells |
title_fullStr | A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells |
title_full_unstemmed | A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells |
title_short | A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells |
title_sort | vegf-a/sox2/srsf2 network controls vegfr1 pre-mrna alternative splicing in lung carcinoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344584/ https://www.ncbi.nlm.nih.gov/pubmed/30674935 http://dx.doi.org/10.1038/s41598-018-36728-y |
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