State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Cell Biochem. 2012 Dec;113(12):3643-52. doi: 10.1002/jcb.24228.
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.
越来越多的证据表明，癌症干细胞（CSC）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尚不清楚。在这里，我们表明 CSC 中的细胞周期状态和 DNA 损伤反应（DDR）可能有助于它们在遗传毒性损伤中存活。在这项研究中，我们通过流式细胞术从食管癌细胞系 EC9706 中分离出食管癌症干细胞（ECSC），通过侧群（SP）表型发现与非 ECSC 相比，ECSC 优先处于静止状态，并且对 DNA 损伤剂的抵抗力更强。进一步的研究表明，ECSC 表达较低水平的 EGFR、磷酸化 Stat3 和 c-Myc，但异常上调 p27。更有趣的是，与非 ECSC 不同，当受到 DNA 损伤剂时，ECSC 显示出减弱的 DDR 以及降低的 DNA 修复潜力。这些数据表明，ECSC 可能利用受损的 DDR 来处理严重的基因组损伤。总之，我们推断 ECSC 的抗损伤能力可能归因于它们的缓慢循环状态和避免由过度 DDR 触发的细胞凋亡或衰老。
