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Dev Cell. 2017 Jun 19;41(6):638-651.e5. doi: 10.1016/j.devcel.2017.05.022.

Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System.

Author information

1
Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 76-543, Cambridge, MA 02138, USA. Electronic address: ste@mit.edu.
2
Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
4
Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 76-543, Cambridge, MA 02138, USA.
5
Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 76-543, Cambridge, MA 02138, USA; Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 76-543, Cambridge, MA 02138, USA. Electronic address: angelika@mit.edu.

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.

KEYWORDS:

aneuploidy; cancer; genome instability; immune system; senescence

PMID:
28633018
PMCID:
PMC5536848
DOI:
10.1016/j.devcel.2017.05.022
[Indexed for MEDLINE]
Free PMC Article

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