Chromosome mis-segregation and cytokinesis failure in trisomic human cells

eLife

Jordi Camps¹  Darawalee Wangsa²  Joana C Macedo³  Elsa Logarinho⁴  Aaron J Mattingly⁴  Vera Lima⁵  Joshua M Nicholson⁵  Thomas Ried⁶  Daniela Cimini⁶  Ana M Gomes⁷  Sofia Dória⁷ 

[1] Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Porto, Portugal;Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal;Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, United States;Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal;Department of Biological Sciences, Virginia Tech, Blacksburg, United States;Department of Genetics, Faculdade de Medicina, Universidade do Porto, Porto, Portugal;Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States;

关键词: chromosome;    aneuploidy;    cancer;    mis-segregation;    CIN;    cytokinesis;   

DOI  :  10.7554/eLife.05068

来源: DOAJ

【 摘 要 】

Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer cell line DLD1 (2n = 46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of chromosome mis-segregation compared to their euploid counterparts. Furthermore, cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We showed that up-regulation of SPG20 expression, brought about by trisomy 13 in DLD1+13 and AF+13 cells, is sufficient for the cytokinesis failure phenotype. Overall, our study shows that aneuploidy can induce chromosome mis-segregation. Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by up-regulation of a gene encoded on the aneuploid chromosome.

【 授权许可】

Unknown