Evidence map›Paper›PMID 26317465›Full record

ArticleCell2015

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

David Roulois, Helen Loo Yau, Rajat Singhania, Yadong Wang, Arnavaz Danesh, Shu Yi Shen, Han Han, Gangning Liang, Peter A Jones, Trevor J Pugh and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 972 papers.

0numbers the graph read from it
0cells of the map it votes in
972citing papers in PubMed
46.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

972 citing papers in PubMed, 1,483 citations in OpenAlex.

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  13. Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026
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912 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

David RouloisPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Helen Loo YauPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada.
Rajat SinghaniaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Yadong WangPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Arnavaz DaneshPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Shu Yi ShenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Han HanDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Gangning LiangDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Peter A JonesDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Trevor J PughPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada.
Catherine O'BrienPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada; Department of Surgery, Toronto General Hospital, Toronto, ON M5T 1P5, Canada.
Daniel D De CarvalhoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada. Electronic address: ddecarv@uhnres.utoronto.ca.
Princess Margaret Cancer Centre · CAUniversity Health Network · CAUniversity of Southern California · USToronto General Hospital · CA

Funding

MECHANISMS OF DE NOVO METHYLATION IN CANCERR01CA082422 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI JONES, PETER A · 1999 to 2016
$5.1M
Epigenetic Drivers of Cancer (PQ 10)R01CA170550 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI BAYLIN, STEPHEN B., JONES, PETER A · 2012 to 2015
$2.4M
NCI NIH HHS 5R01CA082422NCI NIH HHS R01 CA082422NCI NIH HHS R01 CA170550
6 · The paper itself

Abstract

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 IRF7. Indeed, disruption of virus recognition pathways, by individually knocking down MDA5, MAVS, or IRF7, inhibits the ability of 5-AZA-CdR to target colorectal CICs and significantly decreases 5-AZA-CdR long-term growth effects. Moreover, transfection of dsRNA into CICs can mimic the effects of 5-AZA-CdR. Together, our results represent a major shift in understanding the anti-tumor mechanisms of DNA-demethylating agents and highlight the MDA5/MAVS/IRF7 pathway as a potentially druggable target against CICs.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAntimetabolites, AntineoplasticAzacitidineCells, CulturedColorectal NeoplasmsDEAD-box RNA HelicasesDecitabineDNA MethylationEndogenous RetrovirusesHumansInterferon-Induced Helicase, IFIH1Interferon Regulatory Factor-7MiceReceptors, Retinoic AcidRNA, Double-StrandedAdaptor Proteins, Signal TransducingAntimetabolites, AntineoplasticAzacitidineDEAD-box RNA HelicasesDecitabineIFIH1 protein, humanInterferon-Induced Helicase, IFIH1Interferon Regulatory Factor-7IRF7 protein, humanMAVS protein, humanPLAAT4 protein, humanReceptors, Retinoic AcidRNA, Double-Stranded

Identifiers

PMID26317465
PMCPMC4843502
OpenAlexW1905278501

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.