Chromosome mis-segregation and cytokinesis failure in trisomic human cells.
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.
Department of Biological Sciences, Virginia Tech, Blacksburg, United States.
Joshua M
JM
Nicholson
Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Joana C
JC
Macedo
Department of Biological Sciences, Virginia Tech, Blacksburg, United States.
Aaron J
AJ
Mattingly
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Darawalee
D
Wangsa
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Jordi
J
Camps
Department of Genetics, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Vera
V
Lima
Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Ana M
AM
Gomes
Department of Genetics, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Sofia
http://orcid.org/0000-0001-9225-9076
S
Dória
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Thomas
T
Ried
Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Elsa
E
Logarinho
Department of Biological Sciences, Virginia Tech, Blacksburg, United States.
Daniela
D
Cimini
D000653:Amniotic Fluid / Q000166:cytology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D025063:Chromosome Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020090:Chromosome Segregation; D002882:Chromosomes, Human, Pair 13 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002897:Chromosomes, Human, Pair 7 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology; D048749:Cytokinesis / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation; D006801:Humans; D007621:Karyotyping; D010641:Phenotype; D011247:Pregnancy; D061251:Primary Cell Culture; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014314:Trisomy / Q000235:genetics* / Q000473:pathology; D000073839:Trisomy 13 Syndrome
D018797:Cell Cycle Proteins; D011506:Proteins; C464787:SPART protein, human
CIN; aneuploidy; cancer; cell biology; chromosome; chromosomes; cytokinesis; genes; human; mis-segregation