Cargando…
Atypical E2Fs inhibit tumor angiogenesis
Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770600/ https://www.ncbi.nlm.nih.gov/pubmed/28925392 http://dx.doi.org/10.1038/onc.2017.336 |
_version_ | 1783293101760053248 |
---|---|
author | Weijts, B G M W Westendorp, B Hien, B T Martínez-López, L M Zijp, M Thurlings, I Thomas, R E Schulte-Merker, S Bakker, W J de Bruin, A |
author_facet | Weijts, B G M W Westendorp, B Hien, B T Martínez-López, L M Zijp, M Thurlings, I Thomas, R E Schulte-Merker, S Bakker, W J de Bruin, A |
author_sort | Weijts, B G M W |
collection | PubMed |
description | Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer. Tumor formation was either induced by application of 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate or by Myc/Ras overexpression. To our surprise, atypical E2Fs suppressed tumor angiogenesis in all three cancer models, which is in a sharp contrast to previous findings showing that atypical E2Fs promote angiogenesis during fetal development in mice and zebrafish. Real-time imaging in zebrafish displayed that fluorescent-labeled blood vessels showed enhanced intratumoral branching in xenografted E2f7/8-deficient neoplasms compared with E2f7/8-proficient neoplasms. DLL4 expression, a key negative inhibitor of vascular branching, was decreased in E2f7/8-deficient neoplastic cells, indicating that E2F7/8 might inhibit intratumoral vessel branching via induction of DLL4. |
format | Online Article Text |
id | pubmed-5770600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-57706002018-01-22 Atypical E2Fs inhibit tumor angiogenesis Weijts, B G M W Westendorp, B Hien, B T Martínez-López, L M Zijp, M Thurlings, I Thomas, R E Schulte-Merker, S Bakker, W J de Bruin, A Oncogene Short Communication Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer. Tumor formation was either induced by application of 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate or by Myc/Ras overexpression. To our surprise, atypical E2Fs suppressed tumor angiogenesis in all three cancer models, which is in a sharp contrast to previous findings showing that atypical E2Fs promote angiogenesis during fetal development in mice and zebrafish. Real-time imaging in zebrafish displayed that fluorescent-labeled blood vessels showed enhanced intratumoral branching in xenografted E2f7/8-deficient neoplasms compared with E2f7/8-proficient neoplasms. DLL4 expression, a key negative inhibitor of vascular branching, was decreased in E2f7/8-deficient neoplastic cells, indicating that E2F7/8 might inhibit intratumoral vessel branching via induction of DLL4. Nature Publishing Group 2018-01-11 2017-09-18 /pmc/articles/PMC5770600/ /pubmed/28925392 http://dx.doi.org/10.1038/onc.2017.336 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Short Communication Weijts, B G M W Westendorp, B Hien, B T Martínez-López, L M Zijp, M Thurlings, I Thomas, R E Schulte-Merker, S Bakker, W J de Bruin, A Atypical E2Fs inhibit tumor angiogenesis |
title | Atypical E2Fs inhibit tumor angiogenesis |
title_full | Atypical E2Fs inhibit tumor angiogenesis |
title_fullStr | Atypical E2Fs inhibit tumor angiogenesis |
title_full_unstemmed | Atypical E2Fs inhibit tumor angiogenesis |
title_short | Atypical E2Fs inhibit tumor angiogenesis |
title_sort | atypical e2fs inhibit tumor angiogenesis |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770600/ https://www.ncbi.nlm.nih.gov/pubmed/28925392 http://dx.doi.org/10.1038/onc.2017.336 |
work_keys_str_mv | AT weijtsbgmw atypicale2fsinhibittumorangiogenesis AT westendorpb atypicale2fsinhibittumorangiogenesis AT hienbt atypicale2fsinhibittumorangiogenesis AT martinezlopezlm atypicale2fsinhibittumorangiogenesis AT zijpm atypicale2fsinhibittumorangiogenesis AT thurlingsi atypicale2fsinhibittumorangiogenesis AT thomasre atypicale2fsinhibittumorangiogenesis AT schultemerkers atypicale2fsinhibittumorangiogenesis AT bakkerwj atypicale2fsinhibittumorangiogenesis AT debruina atypicale2fsinhibittumorangiogenesis |