IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-07824-4.html
   My bibliography  Save this article

Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells

Author

Listed:
  • Hugh S. Gannon

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • Tao Zou

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • Michael K. Kiessling

    (University of Zurich and University Hospital Zürich
    University Hospital Zurich, University of Zurich)

  • Galen F. Gao

    (Broad Institute of Harvard and MIT)

  • Diana Cai

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • Peter S. Choi

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • Alexandru P. Ivan

    (Dana-Farber Cancer Institute)

  • Ilana Buchumenski

    (Bar-Ilan University)

  • Ashton C. Berger

    (Broad Institute of Harvard and MIT)

  • Jonathan T. Goldstein

    (Broad Institute of Harvard and MIT)

  • Andrew D. Cherniack

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • Francisca Vazquez

    (Broad Institute of Harvard and MIT)

  • Aviad Tsherniak

    (Broad Institute of Harvard and MIT)

  • Erez Y. Levanon

    (Bar-Ilan University)

  • William C. Hahn

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT
    Harvard Medical School
    Dana-Farber Cancer Institute)

  • Matthew Meyerson

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT
    Dana-Farber Cancer Institute
    Harvard Medical School)

Abstract

Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased expression of interferon-stimulated genes. Activation of type I interferon signaling in the context of ADAR1 deficiency can induce cell lethality in non-ADAR1-dependent cell lines. ADAR deletion causes activation of the double-stranded RNA sensor, protein kinase R (PKR). Disruption of PKR signaling, through inactivation of PKR or overexpression of either a wildtype or catalytically inactive mutant version of the p150 isoform of ADAR1, partially rescues cell lethality after ADAR1 loss, suggesting that both catalytic and non-enzymatic functions of ADAR1 may contribute to preventing PKR-mediated cell lethality. Together, these data nominate ADAR1 as a potential therapeutic target in a subset of cancers.

Suggested Citation

  • Hugh S. Gannon & Tao Zou & Michael K. Kiessling & Galen F. Gao & Diana Cai & Peter S. Choi & Alexandru P. Ivan & Ilana Buchumenski & Ashton C. Berger & Jonathan T. Goldstein & Andrew D. Cherniack & Fr, 2018. "Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07824-4
    DOI: 10.1038/s41467-018-07824-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-07824-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-07824-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tanaz Sharifnia & Mathias J. Wawer & Amy Goodale & Yenarae Lee & Mariya Kazachkova & Joshua M. Dempster & Sandrine Muller & Joan Levy & Daniel M. Freed & Josh Sommer & Jérémie Kalfon & Francisca Vazqu, 2023. "Mapping the landscape of genetic dependencies in chordoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07824-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.