有丝分裂可通过细胞内吞作用驱动细胞自噬。
Mitosis can drive cell cannibalism through entosis.
作者信息
Durgan Joanne, Tseng Yun-Yu, Hamann Jens C, Domart Marie-Charlotte, Collinson Lucy, Hall Alan, Overholtzer Michael, Florey Oliver
机构信息
The Babraham Institute, Cambridge, United Kingdom.
Memorial Sloan Kettering Cancer Center, New York, United States.
出版信息
Elife. 2017 Jul 11;6:e27134. doi: 10.7554/eLife.27134.
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.
细胞自噬是上皮细胞自相残杀的一种形式,在人类癌症中普遍存在,通常由基质黏附丧失引发。在此,我们报告了人类上皮细胞中由有丝分裂驱动的细胞自噬的另一种机制。有丝分裂细胞自噬受Cdc42调控,Cdc42控制有丝分裂形态。Cdc42缺失增强有丝分裂脱黏附和变圆,这些依赖于RhoA激活且被Rap1抑制模拟的生物物理变化允许随后的细胞自噬发生。有丝分裂细胞自噬在一些人类癌细胞系中持续发生,且有丝分裂指数与原发性人类乳腺肿瘤中的细胞自相残杀相关。贴壁的野生型细胞可有效地作为细胞自噬的宿主,这表明正常上皮细胞可能吞噬并杀死异常分裂的邻居。最后,我们报告紫杉醇可促进有丝分裂变圆及随后的细胞自噬,揭示了这种药物的一种非常规活性。总之,我们的数据揭示了细胞分裂与自相残杀之间的有趣联系,这对癌症和化疗都具有重要意义。