Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System (original) (raw)
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 missegregation 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.
Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System / S. Santaguida, A. Richardson, D. Iyer, O. M'Saad, L. Zasadil, K. Knouse, Y. Wong, N. Rhind, A. Desai, A. Amon. - In: DEVELOPMENTAL CELL. - ISSN 1534-5807. - 41:6(2017), pp. 638-651.
Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System
###### Primo
;Richardson A;Iyer DR;M'Saad O;Zasadil L;Knouse KA;Wong YL;Rhind N;Desai A;Amon A
2017
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 missegregation 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.
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| Santaguida et al., 2017.pdfaccesso aperto Tipologia: Publisher's version/PDF Dimensione 3.47 MB Formato Adobe PDF Visualizza/Apri | 3.47 MB | Adobe PDF | Visualizza/Apri |
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/622936
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