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2017 ; 6
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Mitosis can drive cell cannibalism through entosis
#MMPMID28693721
Durgan J
; Tseng YY
; Hamann JC
; Domart MC
; Collinson L
; Hall A
; Overholtzer M
; Florey O
Elife
2017[Jul]; 6
(ä): ä PMID28693721
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Entosis is a form of epithelial cell cannibalism that is prevalent in human
cancer, typically triggered by loss of matrix adhesion. Here, we report an
alternative mechanism for entosis in human epithelial cells, driven by mitosis.
Mitotic entosis is regulated by Cdc42, which controls mitotic morphology. Cdc42
depletion enhances mitotic deadhesion and rounding, and these biophysical
changes, which depend on RhoA activation and are phenocopied by Rap1 inhibition,
permit subsequent entosis. Mitotic entosis occurs constitutively in some human
cancer cell lines and mitotic index correlates with cell cannibalism in primary
human breast tumours. Adherent, wild-type cells can act efficiently as entotic
hosts, suggesting that normal epithelia may engulf and kill aberrantly dividing
neighbours. Finally, we report that Paclitaxel/taxol promotes mitotic rounding
and subsequent entosis, revealing an unconventional activity of this drug.
Together, our data uncover an intriguing link between cell division and
cannibalism, of significance to both cancer and chemotherapy.