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Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma
Open accessPreprint — published as 10.1038/s41467-023-36124-9 · Paper page
Abstract
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 were identified in patient and mouse GBMs. Partial removal of p16 Ink4a -expressing malignant senescent cells, which make up less than 7 % of the tumor, modified the tumor ecosystem and improved the survival of GBM-bearing mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identified 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.
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Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
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Chemokine signaling via the CXCR2 receptor reinforces senescence
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Metadata
- Authors
- Salam, R., Saliou, A., Bielle, F., Bertrand, M., Antoniewski, C., Carpentier, C., Alentorn, A., Capelle, L., Sanson, M., Huillard, E., Bellenger, L., Guégan, J., & Le Roux, I.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2022-05-19
- Volume
- 14
- Issue
- 1
- Pages
- 441-441
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9883514
- OpenAlex
- W4318219023
- Cited by
- 132
- References
- 6
- Citations by year
- 2026: 31 · 2025: 39 · 2024: 47 · 2023: 13 · 2022: 2
- FWCI
- 23.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Sorbonne Université
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- glioblastoma, cellular senescence, tumor progression, senolytic therapy, p16INK4a, Nrf2, survival prediction, mouse tumor model, adjuvant therapy
- MeSH terms
- Animals, Female, Gene Expression Regulation, Glioblastoma, Phenotype, Cellular Senescence, Ecosystem, Cyclin-Dependent Kinase Inhibitor p16, Mice
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