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Cited 5 time in webofscience Cited 6 time in scopus
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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, JungHeeShin, JiHyeKim, EungSamLee, NamgyuPark, JinYoungKoo, BonikSamuelHong, SunMiPark, ChangWookChoi, 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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최관용CHOI, KWAN YONG
Div of Integrative Biosci & Biotech
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