Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System.
Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System.
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DOI：
10.1016/j.devcel.2017.05.022
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发表时间：
2017-06-19
影响因子：
11.8
通讯作者：
Amon A
中科院分区：
文献类型：
--
作者：
Santaguida S;Richardson A;Iyer DR;M'Saad O;Zasadil L;Knouse KA;Wong YL;Rhind N;Desai A;Amon A
非整倍体，一种核型不平衡的状态，是癌症的一个标志。染色体拷贝数的变化已被提出通过调节癌症驱动基因的剂量和促进癌症基因组进化来驱动疾病。考虑到核型异常的细胞有可能癌变，是否存在限制这种细胞流行的途径？通过研究非整倍体对细胞生理的直接影响，我们确定了消除非整倍体细胞的机制。我们发现染色体错误分离导致进一步的基因组不稳定，最终导致细胞周期停滞。我们进一步表明，具有复杂核型的细胞表现出衰老的特征，并产生促炎信号，促进免疫系统清除它们。我们提出，核型异常的细胞产生一个信号，为自己的消除，可能作为一种手段，癌细胞免疫监视。
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 exist that limit the prevalence of such cells? 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.
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DOI：
10.1038/nrm2718
发表时间：
2009-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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影响因子：
13.6
作者：
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DOI：
10.1084/jem.20130783
发表时间：
2013-09-23
期刊：
The Journal of experimental medicine
影响因子：
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通讯作者：
Raulet DH
影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
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Elledge SJ
影响因子：
21.3
作者：
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