Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos.
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.
Vitale
Ilio
I
INSERM, Villejuif, France.
Senovilla
Laura
L
Jemaà
Mohamed
M
Michaud
Mickaël
M
Galluzzi
Lorenzo
L
Kepp
Oliver
O
Nanty
Lisa
L
Criollo
Alfredo
A
Rello-Varona
Santiago
S
Manic
Gwenola
G
Métivier
Didier
D
Vivet
Sonia
S
Tajeddine
Nicolas
N
Joza
Nicholas
N
Valent
Alexander
A
Castedo
Maria
M
Kroemer
Guido
G
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*
D016159:Tumor Suppressor Protein p53