Quiescence and attenuated DNA damage response promote survival of esophageal cancer stem cells.
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.
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yulin
Y
Chen
Dan
D
Li
Dapeng
D
Wang
Xuefeng
X
Liu
Ning
N
Yin
Yongmei
Y
Song
Shih Hsin
SH
Lu
Zhenyu
Z
Ju
Qimin
Q
Zhan
D017209:Apoptosis; D001562:Benzimidazoles; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D018920:Coculture Techniques; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D014466:Ultraviolet Rays
D001562:Benzimidazoles; D004273:DNA, Neoplasm; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C017807:bisbenzimide ethoxide trihydrochloride; D002945:Cisplatin