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TP53 drives invasion through expression of its Δ133p53β variant

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Cite this article as: eLife 2016;5:e14734 doi: 10.7554/eLife.14734

Abstract

TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of TP53 mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53. Endogenous mutant Δ133p53β depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant Δ133p53β induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.

Article and author information

Author details

  1. Gilles Gadea

    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Nikola Arsic

    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Kenneth Fernandes

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexandra Diot

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Sébastien M Joruiz

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Samer Abdallah

    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Valerie Meuray

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Stéphanie Vinot

    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Christelle Anguille

    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Judit Remenyi

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Marie P Khoury

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Philip R Quinlan

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Colin A Purdie

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Lee B Jordan

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Frances V Fuller-Pace

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5859-2932
  16. Marion de Toledo

    Université Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  17. Maïlys Cren

    Université Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  18. Alastair M Thompson

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  19. Jean-Christophe Bourdon

    Division of Cancer Research, University of Dundee, Dundee, United Kingdom
    For correspondence
    j.bourdon@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  20. Pierre Roux

    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier, Montpellier, France
    For correspondence
    pierre.roux@crbm.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0671-5413

Funding

Breast Cancer Campaign (2012MaySF127)

  • Jean-Christophe Bourdon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Samples were examined following Local Research EthicsCommittee approval under delegated authority by the Tayside Tissue Bank(www.taysidetissuebank.org).

Reviewing Editor

  1. Joaquín M Espinosa, University of Colorado School of Medicine, United States

Publication history

  1. Received: January 29, 2016
  2. Accepted: September 13, 2016
  3. Accepted Manuscript published: September 15, 2016 (version 1)
  4. Version of Record published: October 17, 2016 (version 2)
  5. Version of Record updated: March 30, 2017 (version 3)

Copyright

© 2016, Gadea et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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