p53-dependent elimination of aneuploid mitotic offspring by entosis.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
22
04
2020
accepted:
12
10
2020
pubmed:
29
10
2020
medline:
16
12
2021
entrez:
28
10
2020
Statut:
ppublish
Résumé
Entosis was proposed to promote aneuploidy and genome instability by cell-in-cell mediated engulfment in tumor cells. We reported here, in epithelial cells, that entosis coupled with mitotic arrest functions to counteract genome instability by targeting aneuploid mitotic progenies for engulfment and elimination. We found that the formation of cell-in-cell structures associated with prolonged mitosis, which was sufficient to induce entosis. This process was controlled by the tumor suppressor p53 (wild-type) that upregulates Rnd3 expression in response to DNA damages associated with prolonged metaphase. Rnd3-compartmentalized RhoA activities accumulated during prolonged metaphase to drive cell-in-cell formation. Remarkably, this prolonged mitosis-induced entosis selectively targets non-diploid progenies for internalization, blockade of which increased aneuploidy. Thus, our work uncovered a heretofore unrecognized mechanism of mitotic surveillance for entosis, which eliminates newly born abnormal daughter cells in a p53-dependent way, implicating in the maintenance of genome integrity.
Identifiants
pubmed: 33110215
doi: 10.1038/s41418-020-00645-3
pii: 10.1038/s41418-020-00645-3
pmc: PMC7862607
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
RHOA protein, human
124671-05-2
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
799-813Références
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