2. Academic Validation
  3. p53-dependent elimination of aneuploid mitotic offspring by entosis

p53-dependent elimination of aneuploid mitotic offspring by entosis

  • Cell Death Differ. 2021 Feb;28(2):799-813. doi: 10.1038/s41418-020-00645-3.
Jianqing Liang  # 1 2,  Zubiao Niu  # 1,  Bo Zhang  # 1 3,  Xiaochen Yu  # 1,  You Zheng 1,  Chenxi Wang 1,  He Ren 1 3,  Manna Wang 1 4,  Banzhan Ruan 1,  Hongquan Qin 1 4,  Xin Zhang 1 5,  Songzhi Gu 1,  Xiaoyong Sai 6,  Yanhong Tai 7,  Lihua Gao 1,  Li Ma 4,  Zhaolie Chen 1,  Hongyan Huang 8,  Xiaoning Wang 9,  Qiang Sun 10
Affiliations

Affiliations

  • 1 Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing, 100071, China.
  • 2 State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, 2005 Songhu Road, Shanghai, 200438, China.
  • 3 Department of Oncology, Beijing Shijitan Hospital of Capital Medical University, 10 TIEYI Road, Beijing, 100038, China.
  • 4 Institute of Molecular Immunology, Southern Medical University, Guangzhou, 510515, China.
  • 5 Department of Pediatric Hematology and Oncology, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
  • 6 National Clinic Center of Geriatric & the State Key Laboratory of Kidney, the Chinese PLA General Hospital, Beijing, 100853, China.
  • 7 The 307 Hospital, 8 Dongda Street, Beijing, 100071, China.
  • 8 Department of Oncology, Beijing Shijitan Hospital of Capital Medical University, 10 TIEYI Road, Beijing, 100038, China. [email protected].
  • 9 National Clinic Center of Geriatric & the State Key Laboratory of Kidney, the Chinese PLA General Hospital, Beijing, 100853, China. [email protected].
  • 10 Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing, 100071, China. [email protected].
  • # Contributed equally.
PMID: 33110215 DOI: 10.1038/s41418-020-00645-3
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.

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