Mitosis can drive cell cannibalism through entosis

被引：88

作者：

Durgan, Joanne ^{[1
,2
]}

Tseng, Yun-Yu ^{[2
,3
]}

Hamann, Jens C. ^{[2
,4
]}

Domart, Marie-Charlotte ^{[5
]}

Collinson, Lucy ^{[5
]}

Hall, Alan ^{[2
]}

Overholtzer, Michael ^{[2
]}

Florey, Oliver ^{[1
]}

机构：

[1] Babraham Inst, Cambridge, England

[2] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[3] Cornell Univ, Weill Grad Sch Med Sci, New York, NY 10021 USA

[4] Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY USA

[5] Francis Crick Inst, London, England

来源：

ELIFE | 2017年 / 6卷

基金：

英国医学研究理事会;

关键词：

SPINDLE ORIENTATION; JUNCTION FORMATION; ACTOMYOSIN CORTEX; DEATH PROCESS; RHO GTPASES; CDC42; SHAPE; MECHANISMS; RETRACTION; CARCINOMA;

D O I：

10.7554/eLife.27134

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 Rapt 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.

引用

页数：26

共 71 条

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