Mitosis can drive cell cannibalism through entosis
Open accessAbstract
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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A specific form of entosis occurring in cancer cells during mitosis, entotic mitosis, is driven by aberrant mitotic rounding in conditions of CDC42 depletion or upon exposure to antimitotic agents.
“a recent study suggests the existence of a specific form of entosis occurring in cancer cells during mitosis (entotic mitosis), which is driven by aberrant mitotic rounding (and thus reduced adhesion) in conditions of cell division cycle 42 (CDC42) depletion or upon exposure to antimitotic agents [698].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [698]
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References 70 · Cited by 117
- Authors
- Durgan, J., Tseng, Y.-Y., Hamann, J. C., Domart, M.-C., Collinson, L., Hall, A., Overholtzer, M., & Florey, O.
- Affiliations
- Babraham Institute (GB)
- Memorial Sloan Kettering Cancer Center (US)
- The Francis Crick Institute (GB)
- Corresponding author
- Florey, Oliver
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-07-11
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5505699
- OpenAlex
- W2736017442
- Cited by
- 117
- References
- 70
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 18 · 2023: 16 · 2022: 13 · 2021: 12 · 2020: 9 · 2019: 14 · 2018: 11 · 2017: 4
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Cancer Research UK (CA47718/A16337, MR/K01580X/1)
- Revson Senior Fellowship
- Marie-Curie Fellowship (624161)
- L'Oreal & UNESCO UK and Ireland
- National Cancer Institute (RO1CA154649)
- Medical Research Council (MR/K01580X/1)
- Wellcome (MR/K01580X/1)
- Biotechnology and Biological Sciences Research Council (MR/K01580X/1)
- Engineering and Physical Sciences Research Council (MR/K01580X/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- entosis, cell cannibalism, mitosis, Cdc42, RhoA, Rap1, epithelial cells, breast cancer, paclitaxel, cell division
- MeSH terms
- Cells, Cultured, Epithelial Cells, Humans, Mitosis, cdc42 GTP-Binding Protein, Entosis, Cytophagocytosis
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