Mitosis Can Drive Cell Cannibalism Through Entosis

Overview

Journal Elife

Specialty Biology

Date 2017 Jul 12

PMID 28693721

Citations 62

Authors

Joanne Durgan

Yun-Yu Tseng

Jens C Hamann

Marie-Charlotte Domart

Lucy Collinson

Alan Hall

Michael Overholtzer

Oliver Florey

Affiliations

Soon will be listed here.

Abstract

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.

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