Quiescence and attenuated DNA damage response promote survival of esophageal cancer stem cells
Authors: Dapeng Wang
Zhenyu Ju
Yulin Chen
Xuefeng Liu
Ning Yin
Dan Li
Shih Hsin Lu
Qimin Zhan
Yongmei Song
Journal: Journal of Cellular Biochemistry (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cancer stem cells; DNA damage response; ECSCs; quiescent; resistance
Affiliations: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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. 

Retracted: No

PubPeer comments:
 Figure 2A: Red boxes of the colony formation assay appear to look quite similar. ![file] , 
 Dear Takifugu Stictonotus, Thank you for your interest of our study and pointing this mistake out. We have rechecked our original data and found that duplicated image in Figure 2A was due to a copy-and-paste error. The original image from that experiment is shown below. This error doesnu2019t change the result and conclusion. We have contacted the Office of the Journal for the figure correction and the correction has been approved. We apologize for any confusion it may have caused. Again many thanks for your comment. Yulin Chen , 
 Corrected Fig.2A ![file] , 
 Corrigendum [28 October 2020] . -------------------------------------------- In the original version of this published article, the authors mistakenly duplicated one of the images in Figure 2A due to a copyu2010andu2010paste error. The correct image from that experiment is shown below. This correction does not change the result and conclusion. We apologize for any confusion it may have caused. ![] In addition, in Figure 2B, by mistake, the data were not calculated from the experiment which was presented in Figure 2A (cell line EC9706), but from a related experiment which we conducted on another esophageal cancer cell line, KYSE150. The reason for using KYSE150 for a similar experiment as we did with EC9706 was that we wanted to confirm our conclusion from multiple cell lines not only from EC9706. The present data from KYSE150 in Figure 2B showed a similar significant difference in SP and nonu2010SP cells in response to IRu2010induced DNA damage, demonstrating that SP cells from KYSE150 were also resistant to DNA damage induced reduction in colony formation. The data from KYSE150 supported very well our conclusions in the paper. However, to make the data more uniform, we decided to only present the data from EC9706. The correct data and graph that were calculated from the exact same experiment on EC9706 presented in Figure 2A is shown below. This correction does not change the result and conclusion. We apologize for any confusion it may have caused. ![] ,