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.

Entosis 被提议通过细胞中细胞介导的吞噬肿瘤细胞来促进非整倍性和基因组不稳定性。我们在此报道，在上皮细胞中，嵌入与有丝分裂停滞相结合，通过靶向非整倍体有丝分裂后代的吞噬和消除来抵消基因组不稳定性。我们发现细胞中细胞结构的形成与有丝分裂延长有关，这足以诱导嵌顿。这个过程由肿瘤抑制因子 p53（野生型）控制，它上调 Rnd3 表达以响应与延长中期相关的 DNA 损伤。Rnd3 分隔的 RhoA 活动在延长的中期积累以驱动细胞内细胞的形成。值得注意的是，这种延长的有丝分裂诱导的嵌入选择性地靶向非二倍体后代进行内化，阻断其中增加了非整倍性。因此，我们的工作揭示了迄今为止未被认识的嵌顿有丝分裂监测机制，它以 p53 依赖性方式消除新生的异常子细胞，与维持基因组完整性有关。