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Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883514/ https://www.ncbi.nlm.nih.gov/pubmed/36707509 http://dx.doi.org/10.1038/s41467-023-36124-9 |
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author | Salam, Rana Saliou, Alexa Bielle, Franck Bertrand, Mathilde Antoniewski, Christophe Carpentier, Catherine Alentorn, Agusti Capelle, Laurent Sanson, Marc Huillard, Emmanuelle Bellenger, Léa Guégan, Justine Le Roux, Isabelle |
author_facet | Salam, Rana Saliou, Alexa Bielle, Franck Bertrand, Mathilde Antoniewski, Christophe Carpentier, Catherine Alentorn, Agusti Capelle, Laurent Sanson, Marc Huillard, Emmanuelle Bellenger, Léa Guégan, Justine Le Roux, Isabelle |
author_sort | Salam, Rana |
collection | PubMed |
description | Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16(Ink4a)-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM. |
format | Online Article Text |
id | pubmed-9883514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98835142023-01-29 Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma Salam, Rana Saliou, Alexa Bielle, Franck Bertrand, Mathilde Antoniewski, Christophe Carpentier, Catherine Alentorn, Agusti Capelle, Laurent Sanson, Marc Huillard, Emmanuelle Bellenger, Léa Guégan, Justine Le Roux, Isabelle Nat Commun Article Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16(Ink4a)-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM. Nature Publishing Group UK 2023-01-27 /pmc/articles/PMC9883514/ /pubmed/36707509 http://dx.doi.org/10.1038/s41467-023-36124-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Salam, Rana Saliou, Alexa Bielle, Franck Bertrand, Mathilde Antoniewski, Christophe Carpentier, Catherine Alentorn, Agusti Capelle, Laurent Sanson, Marc Huillard, Emmanuelle Bellenger, Léa Guégan, Justine Le Roux, Isabelle Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma |
title | Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma |
title_full | Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma |
title_fullStr | Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma |
title_full_unstemmed | Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma |
title_short | Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma |
title_sort | cellular senescence in malignant cells promotes tumor progression in mouse and patient glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883514/ https://www.ncbi.nlm.nih.gov/pubmed/36707509 http://dx.doi.org/10.1038/s41467-023-36124-9 |
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