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Journal of Cellular Biochemistry

Quiescence and attenuated DNA damage response promote survival of esophageal cancer stem cells

Authors

  • Yulin Chen,

    1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Dan Li,

    1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Dapeng Wang,

    1. Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
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  • Xuefeng Liu,

    1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Ning Yin,

    1. Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
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  • Yongmei Song,

    1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Shih Hsin Lu,

    1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Zhenyu Ju,

    1. Max-Planck-Partner Group on Stem Cell Aging, Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, China
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  • Qimin Zhan

    Corresponding author
    1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    • Director and Professor, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
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Abstract

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: 3643–3652, 2012. © 2012 Wiley Periodicals, Inc.

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