Quiescence and attenuated DNA damage response promote survival of esophageal cancer stem cells
Quiescence and attenuated DNA damage response promote survival of esophageal cancer stem cells
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DOI：
10.1002/jcb.24228
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Zhan, Qimin
中科院分区：
文献类型：
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作者：
Chen, Yulin;Li, Dan;Zhan, Qimin
越来越多的证据表明，肿瘤干细胞（CSCs）具有抵抗DNA损伤诱导的细胞死亡的能力，但其机制在很大程度上是未知的。在这里，我们表明，细胞周期状态和DNA损伤反应（DDR）在CSC可能有助于他们的生存在遗传毒性的侮辱。在这项研究中，我们通过流式细胞术从食管癌细胞系EC 9706中分离出食管癌干细胞（ECSCs），通过侧群（SP）表型，发现ECSCs优先保持静止相比，非ECSCs，更耐DNA损伤剂。进一步的研究显示，ECSC表达较低水平的EGFR、磷酸化Stat 3和c-Myc，但异常上调p27。更有趣的是，与非ECSC不同，当遭受DNA损伤剂时，ECSC显示减弱的DDR，以及下降的DNA修复潜力。这些数据表明，ECSC可能采用受损的DDR来处理严重的基因组损伤。总之，我们推断ECSCs的抗损伤能力可能归因于它们的慢循环状态和避免由过量DDR引发的凋亡或衰老。J.细胞。113：36433652，2012。(C)2012 Wiley Periodicals，Inc.
Accumulating evidence indicates cancer stem cells (CSCs) possess the capability to resist DNA-damage induced cell death, whereas the mechanism is largely unknown. Here we show that cell cycle status and DNA damage response (DDR) in CSCs probably contribute to their survival in genotoxic insults. In this study, we isolated esophageal cancer stem cells (ECSCs) from esophageal cancer cell line EC9706 by side-population (SP) phenotype through flow cytometry and found that ECSCs preferentially stay quiescent as compared to the non-ECSCs and are more resistant to DNA damage agents. Further study revealed that ECSCs express a lower level of EGFR, phosphoralated Stat3, and c-Myc, yet abnormally upregulated p27. More interestingly, different from non-ECSCs, when suffering DNA damage agents, ECSCs showed attenuated DDR, as well as declined DNA repair potential. These data indicated ECSCs probably employed an impaired DDR to handle severe genomic insults. Conclusively, we infer that the damage-resistance ability of ECSCs is likely attributed to their slow-cycling status and avoidance of apoptosis or senescence triggered by an excessive DDR. J. Cell. Biochem. 113: 36433652, 2012. (C) 2012 Wiley Periodicals, Inc.