Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System
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 cancero...
| Main Authors: | , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Published: |
Elsevier BV
2018
|
| Online Access: | http://hdl.handle.net/1721.1/116548 https://orcid.org/0000-0002-1501-6190 https://orcid.org/0000-0003-0649-7428 https://orcid.org/0000-0001-9837-0314 |
| _version_ | 1826190217745268736 |
|---|---|
| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 |
| author_sort | Richardson, Amelia |
| collection | MIT |
| description | 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 |
| first_indexed | 2024-09-23T08:36:52Z |
| format | Article |
| id | mit-1721.1/116548 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:36:52Z |
| publishDate | 2018 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1165482022-09-30T09:59:25Z Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System 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 Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Santaguida, Stefano M'Saad, Ons Zasadil, Lauren M Knouse, Kristin Ann Amon, Angelika B 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 National Institutes of Health (U.S.) (Grant CA206157) National Institutes of Health (U.S.) (Grant GM118066) National Institute of General Medical Sciences (U.S.) (Grant T32GM007753) 2018-06-25T14:11:51Z 2018-06-25T14:11:51Z 2017-06 2017-03 2018-06-22T17:20:44Z Article http://purl.org/eprint/type/JournalArticle 1534-5807 1878-1551 http://hdl.handle.net/1721.1/116548 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 https://orcid.org/0000-0002-1501-6190 https://orcid.org/0000-0003-0649-7428 https://orcid.org/0000-0001-9837-0314 http://dx.doi.org/10.1016/J.DEVCEL.2017.05.022 Developmental Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | 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 Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System |
| title | Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System |
| title_full | Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System |
| title_fullStr | Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System |
| title_full_unstemmed | Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System |
| title_short | Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System |
| title_sort | chromosome mis segregation generates cell cycle arrested cells with complex karyotypes that are eliminated by the immune system |
| url | http://hdl.handle.net/1721.1/116548 https://orcid.org/0000-0002-1501-6190 https://orcid.org/0000-0003-0649-7428 https://orcid.org/0000-0001-9837-0314 |
| work_keys_str_mv | AT richardsonamelia chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT iyerdivyaramalingam chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT wongyaoliang chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT rhindnicholas chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT desaiarshad chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT santaguidastefano chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT msaadons chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT zasadillaurenm chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT knousekristinann chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem AT amonangelikab chromosomemissegregationgeneratescellcyclearrestedcellswithcomplexkaryotypesthatareeliminatedbytheimmunesystem |