DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts

@article{Roulois2015DNADemethylatingAT,
  title={DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts},
  author={David Roulois and Helen Loo Yau and Rajat Singhania and Yadong Wang and Arnavaz Danesh and Shu Yi Shen and Han Han and Gangning Liang and Peter A. Jones and Trevor J. Pugh and Catherine A. O’Brien and Daniel Diniz de Carvalho},
  journal={Cell},
  year={2015},
  volume={162},
  pages={961-973}
}
DNA-demethylating agents have shown clinical anti-tumor efficacy via an unknown mechanism of action. Using a combination of experimental and bioinformatics analyses in colorectal cancer cells, we demonstrate that low-dose 5-AZA-CdR targets colorectal cancer-initiating cells (CICs) by inducing viral mimicry. This is associated with induction of dsRNAs derived at least in part from endogenous retroviral elements, activation of the MDA5/MAVS RNA recognition pathway, and downstream activation of… CONTINUE READING
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