Mitosis can drive cell cannibalism through entosis
Joanne Durgan,
Yun-Yu Tseng,
Jens C Hamann,
Marie-Charlotte Domart,
Lucy Collinson,
Alan Hall,
Michael Overholtzer,
Oliver Florey
Affiliations
Joanne Durgan
The Babraham Institute, Cambridge, United Kingdom; Memorial Sloan Kettering Cancer Center, New York, United States
Yun-Yu Tseng
Memorial Sloan Kettering Cancer Center, New York, United States; Weill Graduate School of Medical Sciences, Cornell University, New York, United States
Jens C Hamann
Memorial Sloan Kettering Cancer Center, New York, United States; Louis V Gerstner Jr Graduate School of Biomedical Sciences, New York, United States
Marie-Charlotte Domart
The Francis Crick Institute, London, United Kingdom
Lucy Collinson
The Francis Crick Institute, London, United Kingdom
Alan Hall
Memorial Sloan Kettering Cancer Center, New York, United States
Michael Overholtzer
Memorial Sloan Kettering Cancer Center, New York, United States
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.
