Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos |
| |
Authors: | Ilio Vitale Laura Senovilla Mohamed Jemaà Mickaël Michaud Lorenzo Galluzzi Oliver Kepp Lisa Nanty Alfredo Criollo Santiago Rello‐Varona Gwenola Manic Didier Métivier Sonia Vivet Nicolas Tajeddine Nicholas Joza Alexander Valent Guido Kroemer |
| |
Affiliation: | 1. INSERM, Villejuif, France;2. Institut Gustave Roussy, Villejuif, France;3. Faculté de Médecine, Université Paris‐Sud XI, Villejuif, France;4. Unité de Recherche Translationnelle, Institut Gustave Roussy, Villejuif, France |
| |
Abstract: | 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. |
| |
Keywords: | aneuploidy apoptosis centrosome colon carcinoma mitotic catastrophe |
|
|