Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos
Open accessAbstract
Tetraploidy can constitute a metastable intermediate between normal diploidy and oncogenic aneuploidy. Here, we show that the absence of p53 is not only permissive for the survival but also for multipolar asymmetric divisions of tetraploid cells, which lead to the generation of aneuploid cells with a near-to-diploid chromosome content. Multipolar mitoses (which reduce the tetraploid genome to a sub-tetraploid state) are more frequent when p53 is downregulated and the product of the Mos oncogene is upregulated. Mos inhibits the coalescence of supernumerary centrosomes that allow for normal bipolar mitoses of tetraploid cells. In the absence of p53, Mos knockdown prevents multipolar mitoses and exerts genome-stabilizing effects. These results elucidate the mechanisms through which asymmetric cell division drives chromosomal instability in tetraploid cells.
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Mitotic defects can derive from exogenous xenobiotics and endogenous replication/mitotic stress.
“Mitotic defects can derive from: (1) exogenous sources, including a large panel of xenobiotics that alter DNA replication, cell cycle checkpoints, chromosome segregation, and/or microtubular dynamics [976]; or (2) endogenous sources, such as high levels of DNA replication stress or mitotic stress caused by an aberrant ploidy or by deregulated expression/activity of factors involved in DNA”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [978]
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References 67 · Cited by 146
- Authors
- Vitale, I., Senovilla, L., Jemaà, M., Michaud, M., Galluzzi, L., Kepp, O., Nanty, L., Criollo, A., Rello‐Varona, S., Manic, G., Métivier, D., Vivet, S., Tajeddine, N., Joza, N., Valent, A., Castedo, M., & Kroemer, G.
- Affiliations
- Université Paris-Sud (FR)
- Institut Gustave Roussy (FR)
- Corresponding author
- Kroemer, Guido
- ORCID
- Venue
- The EMBO Journal
- Published
- 2010-02-25
- Volume
- 29
- Issue
- 7
- Pages
- 1272-1284
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2857458
- OpenAlex
- W2025702938
- Cited by
- 146
- References
- 67
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 9 · 2022: 5 · 2021: 6 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 11 · 2016: 8 · 2015: 8 · 2014: 10 · 2013: 22 · 2012: 14
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- European Commission
- Institut National Du Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- tetraploidy, multipolar mitosis, p53, asymmetric cell division, supernumerary centrosomes, aneuploidy, chromosomal instability, genome stability
- MeSH terms
- Aneuploidy, Animals, Carcinoma, Colonic Neoplasms, Female, Humans, Mice, Nude, Mitosis, Polyploidy, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Genes, mos, Gene Deletion, Centrosome, Chromosomal Instability, Cell Line, Tumor, Mice
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