Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System
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Author(s)
Richardson, Amelia
Iyer, Divya Ramalingam
Wong, Yao Liang
Rhind, Nicholas
Desai, Arshad
Santaguida, Stefano
M'Saad, Ons
Zasadil, Lauren M
Knouse, Kristin Ann
Amon, Angelika B
Date Issued
June 2017
Journal
Developmental Cell
Publisher
Elsevier BV
Citation
Santaguida, Stefano et al. “Chromosome Mis-Segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes That Are Eliminated by the Immune System.” Developmental Cell 41, 6 (June 2017): 638–651 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways that limit the prevalence of such cells exist? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to further genomic instability that ultimately causes cell-cycle arrest. We further show that cells with complex karyotypes exhibit features of senescence and produce pro-inflammatory signals that promote their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that may serve as a means for cancer cell immunosurveillance. By examining the immediate consequences of chromosome mis-segregation, Santaguida et al. show that aneuploidy causes genomic instability and the evolution of cells with complex karyotypes. Such cells undergo senescence and produce pro-inflammatory cytokines that promote their clearance by natural killer cells. Keywords: aneuploidy; cancer; immune system; genome instability; senescence
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.DEVCEL.2017.05.022
