Document Type
Article
Publication Date
1-5-2023
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.
Recommended Citation
Sterling, Noelle A; Park, Jun Young; Park, Raehee; Cho, Seo-Hee; and Kim, Seonhee, "An Entosis-Like Process Induces Mitotic Disruption in Pals1 Microcephaly Pathogenesis" (2023). Center for Translational Medicine Faculty Papers. Paper 106.
https://jdc.jefferson.edu/transmedfp/106
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
36604424
Language
English
Comments
This article is the author’s final published version in Nature Communications, Volume 14, Issue 1, January 2023, Article number 82.
The published version is available at https://doi.org/10.1038/s41467-022-35719-y. Copyright © Sterling et al.