IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v462y2009i7269d10.1038_nature08460.html
   My bibliography  Save this article

Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1

Author

Listed:
  • David A. Barbie

    (Department of Medical Oncology,
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA)

  • Pablo Tamayo

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Jesse S. Boehm

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • So Young Kim

    (Department of Medical Oncology,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115 USA)

  • Susan E. Moody

    (Department of Medical Oncology,
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Ian F. Dunn

    (Department of Medical Oncology,
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Department of Neurosurgery,)

  • Anna C. Schinzel

    (Department of Medical Oncology,
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Peter Sandy

    (M.I.T., 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Koch Institute for Integrative Cancer Research, 40 Ames Street, Cambridge, Massachusetts 02142, USA)

  • Etienne Meylan

    (M.I.T., 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Koch Institute for Integrative Cancer Research, 40 Ames Street, Cambridge, Massachusetts 02142, USA)

  • Claudia Scholl

    (Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Stefan Fröhling

    (Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Edmond M. Chan

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Martin L. Sos

    (Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Köln, Gleueler Str. 50, 50931 Köln, Germany)

  • Kathrin Michel

    (Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Köln, Gleueler Str. 50, 50931 Köln, Germany)

  • Craig Mermel

    (Department of Medical Oncology,
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Serena J. Silver

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Barbara A. Weir

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Jan H. Reiling

    (M.I.T., 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Whitehead Institute of Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Qing Sheng

    (Department of Medical Oncology,)

  • Piyush B. Gupta

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Raymond C. Wadlow

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA)

  • Hanh Le

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Sebastian Hoersch

    (Koch Institute for Integrative Cancer Research, 40 Ames Street, Cambridge, Massachusetts 02142, USA)

  • Ben S. Wittner

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA)

  • Sridhar Ramaswamy

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA)

  • David M. Livingston

    (Department of Medical Oncology,)

  • David M. Sabatini

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    M.I.T., 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Whitehead Institute of Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA)

  • Matthew Meyerson

    (Department of Medical Oncology,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115 USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Roman K. Thomas

    (Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Köln, Gleueler Str. 50, 50931 Köln, Germany
    University of Köln, Gleueler Str. 50, 50931 Köln, Germany
    Chemical Genomics Center of the Max-Planck-Society, Otto-Hahn-Str. 15, 44227 Dortmund, Germany)

  • Eric S. Lander

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    M.I.T., 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA)

  • Jill P. Mesirov

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • David E. Root

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • D. Gary Gilliland

    (Department of Medical Oncology,
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA)

  • Tyler Jacks

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    M.I.T., 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Koch Institute for Integrative Cancer Research, 40 Ames Street, Cambridge, Massachusetts 02142, USA
    Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA)

  • William C. Hahn

    (Department of Medical Oncology,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115 USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA)

Abstract

Targeting KRAS cancers Mutations in genes of the RAS family are preset on about 20% of human cancers, making RAS proteins prime potential targets for cancer therapy. Direct targeting of RAS proteins has not so far been productive, but two papers published in this issue offer the prospect of alternative targets in a signalling pathway downstream of RAS. Using a synthetic lethality RNAi screen, Barbie et al. identify TBK1 as a kinase in the NF-κB signalling pathway that is essential for the survival of KRAS-transformed cells. TBK1 induces anti-apoptotic signals and may be a therapeutic cancer target. And in an elegant mouse model for lung cancer driven by Kras mutation and loss of p53, Meylan et al. show that NF-κB signalling is activated by the concerted actions of these two alterations and required for tumour initiation and tumour maintenance.

Suggested Citation

  • David A. Barbie & Pablo Tamayo & Jesse S. Boehm & So Young Kim & Susan E. Moody & Ian F. Dunn & Anna C. Schinzel & Peter Sandy & Etienne Meylan & Claudia Scholl & Stefan Fröhling & Edmond M. Chan & Ma, 2009. "Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1," Nature, Nature, vol. 462(7269), pages 108-112, November.
    • Handle: RePEc:nat:nature:v:462:y:2009:i:7269:d:10.1038_nature08460
    DOI: 10.1038/nature08460
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature08460
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature08460?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    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:nature:v:462:y:2009:i:7269:d:10.1038_nature08460. 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.