Chromosome Instability: Chaos from Within

RESEARCH HIGHLIGHTS

Nature Reviews Cancer | AOP, published online 17 March 2011; doi:10.1038/nrc3048

CHROMOSOME INSTABILITY myosin light chain 2 showed that the internalized cells caused incom- plete formation of the contractile Chaos from within ring in the host cell, explaining why the cleavage furrow and cytokinesis Aneuploidy, the gain or loss of chro- host cell in the interim? In their latest were impeded. mosomes, is thought to primarily work, the authors examined cell- Tetraploidy is a common inter- on balance, arise from mutations that disrupt in-cell structures in primary cancer mediate of aneuploid cell lineages: entosis might be a mitosis or that alter centrosome samples and cell lines, and found that does this progression hold true numbers. However, routes to aneu- multinucleation of entosis host cells for these binucleated host cells? tumour-promoting ploidy might actually be more varied. was tenfold more common compared Fluorescence in situ hybridization for phenomenon Cell fusion has been suggested as an with adjacent single cells. chromosomes 8 and 12 revealed that alternative route, and a new study Time-lapse microscopy was binucleated intermediates of differ- proposes entosis as an important used to track immortalized or fully ent cell lines did produce aneuploid path to aneuploidy without a prior transformed breast and bronchial derivates. requirement for mutations. cell lines over many cell divisions. Confirming previous observa- Entosis was originally identi- This showed that entosis host cells tions, the authors found a positive fied by Michael Overholtzer and frequently failed to undergo cell correlation between cell-in-cell colleagues as a putative tumour- division, directly linking entosis frequency and advancing clinical suppressive mechanism, in which with multinucleation. Entosis host grade of tumour samples, indicating matrix-detached cells are internalized cells that did undergo mitosis that, on balance, entosis might be a into adjacent cells, resulting in cell- showed no disruptions of spindle tumour-promoting phenomenon. in-cell structures. Typically, internal- morphology or prophase to ana- Although entosis can be con- ized cells are eventually degraded to phase duration. However, when sidered as a non-genetic route to end their tumorigenic potential, but the internalized cell was by chance aneuploidy, it will be interesting to what are the consequences to the positioned as a physical barrier to determine whether there are indeed the plane of attempted cancer-relevant mutations that cleavage, failed cyto- predispose to entosis in addition kinesis and binucle- to those, such as the loss of TP53, ated, tetraploid that tolerate the resultant tetraploid cells resulted. Even state and drive its progression to partially internal- aneuploidy. ized cells were Darren J. Burgess found to serve as barriers to cyto- ORIGINAL RESEARCH PAPER Krajcovic, M. et al. A non-genetic route to aneuploidy in human kinesis. Staining cancers. Nature Cell Biol. 13, 324–330 (2011) for phosphorylated