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Mitotic catastrophe: a mechanism for avoiding genomic instability

Abstract

The improper distribution of chromosomes during mitosis compromises cellular functions and can reduce cellular fitness or contribute to malignant transformation. As a countermeasure, higher eukaryotes have developed strategies for eliminating mitosis-incompetent cells, one of which is mitotic catastrophe. Mitotic catastrophe is driven by a complex and poorly understood signalling cascade but, from a functional perspective, it can be defined as an oncosuppressive mechanism that precedes (and is distinct from) apoptosis, necrosis or senescence. Accordingly, the disruption of mitotic catastrophe precipitates tumorigenesis and cancer progression, and its induction constitutes a therapeutic endpoint.

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Figure 1: Morphological aspects of mitotic catastrophe, apoptosis, necrosis and autophagic vacuolization.
Figure 2: Definition and types of mitotic catastrophe.
Figure 3: Consequences of failing mitotic catastrophe.

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Acknowledgements

Electron microscopy pictures in figure 1 were kindly provided by G. Pierron, Institut Gustave Roussy, France. I.V. and L.G. are supported by the Ligue Nationale contre le Cancer and APO-SYS, respectively. G.K. is supported by the Ligue Nationale contre le Cancer (Equipes labellisée), Agence Nationale pour la Recherche, European Commission (Active p53, Apo-Sys, ArtForce, ApopTrain and ChemoRes), Fondation pour la Recherche Médicale, Institut National du Cancer and Cancéropôle Ile-de-France.

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Vitale, I., Galluzzi, L., Castedo, M. et al. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol 12, 385–392 (2011). https://doi.org/10.1038/nrm3115

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