title: Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos.
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.
authors.affiliation: INSERM, Villejuif, France.
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jemaà
authors.forename: Mickaël
authors.initials: M
authors.lastname: Michaud
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Lisa
authors.initials: L
authors.lastname: Nanty
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.forename: Santiago
authors.initials: S
authors.lastname: Rello-Varona
authors.forename: Gwenola
authors.initials: G
authors.lastname: Manic
authors.forename: Didier
authors.initials: D
authors.lastname: Métivier
authors.forename: Sonia
authors.initials: S
authors.lastname: Vivet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tajeddine
authors.forename: Nicholas
authors.initials: N
authors.lastname: Joza
authors.forename: Alexander
authors.initials: A
authors.lastname: Valent
authors.forename: Maria
authors.initials: M
authors.lastname: Castedo
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism; D043171:Chromosomal Instability; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016258:Genes, mos; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D011123:Polyploidy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53