IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms13781.html
   My bibliography  Save this article

A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis

Author

Listed:
  • Ines Jeric

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories)

  • Gabriele Maurer

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories
    Present address: AOP Orphan Pharmaceuticals, 1160 Vienna, Austria)

  • Anna Lina Cavallo

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories
    Present address: AstraZeneca R&D Discovery Sciences RAD, SE-431 83 Mölndal, Sweden)

  • Josipa Raguz

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories)

  • Enrico Desideri

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories)

  • Bartosz Tarkowski

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories
    Present address: Laboratory of Molecular and Cell Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland)

  • Matthias Parrini

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories
    Present address: Institute of Animal Breeding & Genetics, University of Veterinary Medicine, 1210 Vienna, Austria)

  • Irmgard Fischer

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories)

  • Kurt Zatloukal

    (Institute of Pathology, Medical University of Graz)

  • Manuela Baccarini

    (Immune biology, and Genetics, Center for Molecular Biology, University of Vienna—Max F. Perutz Laboratories)

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, but its molecular heterogeneity hampers the design of targeted therapies. Currently, the only therapeutic option for advanced HCC is Sorafenib, an inhibitor whose targets include RAF. Unexpectedly, RAF1 expression is reduced in human HCC samples. Modelling RAF1 downregulation by RNAi increases the proliferation of human HCC lines in xenografts and in culture; furthermore, RAF1 ablation promotes chemical hepatocarcinogenesis and the proliferation of cultured (pre)malignant mouse hepatocytes. The phenotypes depend on increased YAP1 expression and STAT3 activation, observed in cultured RAF1-deficient cells, in HCC xenografts, and in autochthonous liver tumours. Thus RAF1, although essential for the development of skin and lung tumours, is a negative regulator of hepatocarcinogenesis. This unexpected finding highlights the contribution of the cellular/tissue environment in determining the function of a protein, and underscores the importance of understanding the molecular context of a disease to inform therapy design.

Suggested Citation

  • Ines Jeric & Gabriele Maurer & Anna Lina Cavallo & Josipa Raguz & Enrico Desideri & Bartosz Tarkowski & Matthias Parrini & Irmgard Fischer & Kurt Zatloukal & Manuela Baccarini, 2016. "A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13781
    DOI: 10.1038/ncomms13781
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13781
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13781?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
    ---><---

    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:7:y:2016:i:1:d:10.1038_ncomms13781. 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.