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Updated: Dec 3, 2025
Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
p53-dependent elimination of aneuploid mitotic offspring by entosis
Jianqing Liang1,2, Zubiao Niu1, Bo Zhang1,3
1Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing, 100071, China.
Abstract:
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.
Insights
Entosis, a cell-in-cell process, eliminates abnormal daughter cells during prolonged mitosis. This p53-dependent mechanism, involving Rnd3, maintains genome integrity by targeting aneuploid cells.
Area of Science:
- Cell Biology
- Genetics
- Cancer Research
Background:
- Entosis, or cell-in-cell engulfment, has been implicated in promoting aneuploidy and genome instability in tumor cells.
- The precise role of entosis in maintaining genome integrity, particularly in non-cancerous cells, remains incompletely understood.
Purpose of the Study:
- To investigate the function of entosis in epithelial cells, specifically its relationship with mitotic arrest and genome stability.
- To elucidate the molecular mechanisms underlying entosis-mediated elimination of aneuploid cells.
Main Methods:
- Induction of cell-in-cell structures via prolonged mitosis.
- Analysis of p53 and Rnd3 involvement in entosis.
- Assessment of aneuploidy levels following entosis blockade.
Main Results:
- Prolonged mitosis induces entosis in epithelial cells, leading to cell-in-cell structure formation.
- Wild-type p53 upregulates Rnd3 expression in response to DNA damage during prolonged metaphase, driving entosis.
- Entosis selectively engulfs and eliminates aneuploid mitotic progeny, and its blockade increases aneuploidy.
Conclusions:
- Entosis, coupled with mitotic arrest, acts as a novel mitotic surveillance mechanism in epithelial cells.
- This p53-dependent entosis pathway targets and eliminates newly formed aneuploid daughter cells, thereby maintaining genome integrity.
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