REST-dependent expression of TRF2 renders non-neuronal cancer cells resistant to DNA damage during oxidative stress.
SCIE
SCOPUS
- Title
- REST-dependent expression of TRF2 renders non-neuronal cancer cells resistant to DNA damage during oxidative stress.
- Authors
- Kwon, JungHee; Shin, JiHye; Kim, EungSam; Lee, Namgyu; Park, JinYoung; Koo, BonikSamuel; Hong, SunMi; Park, ChangWook; Choi, KY
- Date Issued
- 2013-02-15
- Publisher
- WILEY-LISS
- Abstract
- REST is a neuronal gene silencing factor ubiquitously expressed in non-neuronal tissues. REST is additionally believed to serve as a tumor suppressor in non-neuronal cancers. Conversely, recent findings on REST-dependent tumorigenesis in non-neuronal cells consistently suggest a potential role of REST as a tumor promoter. Here, we have uncovered for the first time the mechanism by which REST contributes to cancer cell survival in non-neuronal cancers. We observed abundant expression of REST in various types of non-neuronal cancer cells compared to normal tissues. The delicate roles of REST were further evaluated in HCT116 and HeLa, non-neuronal cancer cell lines expressing REST. REST silencing resulted in decreased cell survival and activation of the DNA damage response (DDR) through a decrease in the level of TRF2, a telomere-binding protein. These responses were correlated with reduced colony formation ability and accelerated telomere shortening in cancer cells upon the stable knockdown of REST. Interestingly, REST was down-regulated under oxidative stress conditions via ubiquitin proteasome system, suggesting that sustainability of REST expression is critical to determine cell survival during oxidative stress in a tumor microenvironment. Our results collectively indicate that REST-dependent TRF2 expression renders cancer cells resistant to DNA damage during oxidative stress, and mechanisms to overcome oxidative stress, such as high levels of REST or the stress-resistant REST mutants found in specific human cancers, may account for REST-dependent tumorigenesis.
- Keywords
- REST/NRSF; TRF2; oxidative stress; DDR; RESTRICTIVE SILENCER FACTOR; LUNG-CANCER; GENE; REPRESSOR; TELOMERES; APOPTOSIS; TUMOR; DIFFERENTIATION; TRANSFORMATION; REST/NRSF
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/15840
- DOI
- 10.1002/IJC.27741
- ISSN
- 0020-7136
- Article Type
- Article
- Citation
- International Journal of Cancer, vol. 132, no. 4, page. 832 - 842, 2013-02-15
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