한빛사논문
- 조회155
Noelle A. Sterling 1,2, Jun Young Park 1, Raehee Park 1, Seo-Hee Cho 3 & Seonhee Kim 1
1Shriners Hospitals Pediatric Research Center, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
2Biomedical Sciences Graduate Program, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
3Center for Translational Medicine, Department of Medicine, Sydney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Corresponding author : Correspondence to Seonhee Kim.
Abstract
Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing gene Pals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely abrogates CIC structures and restores the normal length of mitosis. Moreover, genetic elimination of Trp53 produces a remarkable rescue of cortical size along with substantial reductions of CIC structures and cell death. These results provide a novel pathogenic mechanism by which microcephaly is produced through entotic cell cannibalism.
논문정보
- Research article
- 2023년 01월 (BRIC 등록일 2023-04-14)
- 국외 연구진
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