1. Cancer Biology
  2. Cell Biology
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p27Kip1 promotes invadopodia turnover and invasion through the regulation of the PAK1/Cortactin pathway

  1. Pauline Jeannot
  2. Ada Nowosad
  3. Renaud T Perchey
  4. Caroline Callot
  5. Evangeline Bennana
  6. Takanori Katsube
  7. Patrick Mayeux
  8. François Guillonneau
  9. Stéphane Manenti
  10. Arnaud Besson  Is a corresponding author
  1. INSERM, France
  2. National Institute of Radiological Sciences, Japan
  3. French Institute of Health and Medical Research, France
Research Article
  • Cited 27
  • Views 1,453
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Cite this article as: eLife 2017;6:e22207 doi: 10.7554/eLife.22207

Abstract

p27Kip1 (p27) is a cyclin-CDK inhibitor and negative regulator of cell proliferation. p27 also controls other cellular processes including migration and cytoplasmic p27 can act as an oncogene. Furthermore, cytoplasmic p27 promotes invasion and metastasis, in part by promoting epithelial to mesenchymal transition. Herein, we find that p27 promotes cell invasion by binding to and regulating the activity of Cortactin, a critical regulator of invadopodia formation. p27 localizes to invadopodia and limits their number and activity. p27 promotes the interaction of Cortactin with PAK1. In turn, PAK1 promotes invadopodia turnover by phosphorylating Cortactin, and expression of Cortactin mutants for PAK-targeted sites abolishes p27's effect on invadopodia dynamics. Thus, in absence of p27, cells exhibit increased invadopodia stability due to impaired PAK1-Cortactin interaction, but their invasive capacity is reduced compared to wild-type cells. Overall, we find that p27 directly promotes cell invasion by facilitating invadopodia turnover via the Rac1/PAK1/Cortactin pathway.

Article and author information

Author details

  1. Pauline Jeannot

    Cancer Research Center of Toulouse, INSERM, Toulouse,, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Ada Nowosad

    Cancer Research Center of Toulouse, INSERM, Toulouse,, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Renaud T Perchey

    Cancer Research Center of Toulouse, INSERM, Toulouse,, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Caroline Callot

    Cancer Research Center of Toulouse, INSERM, Toulouse,, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Evangeline Bennana

    Institut Cochin, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Takanori Katsube

    Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Patrick Mayeux

    Institut Cochin, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. François Guillonneau

    Institut Cochin, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Stéphane Manenti

    Cancer Research Center of Toulouse, INSERM, Toulouse,, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Arnaud Besson

    CRCT UMR 1037 INSERM-Universite Paul Sabatier, French Institute of Health and Medical Research, Toulouse cedex 1, France
    For correspondence
    arnaud.besson@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9599-3943

Funding

Ligue Nationale Contre le Cancer

  • Renaud T Perchey
  • Stéphane Manenti
  • Arnaud Besson

Ministere de l'enseignement superieur et de la recherche

  • Pauline Jeannot
  • Ada Nowosad

INSERM

  • Evangeline Bennana
  • Patrick Mayeux
  • François Guillonneau
  • Stéphane Manenti
  • Arnaud Besson

CNRS

  • Stéphane Manenti
  • Arnaud Besson

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

Reviewing Editor

  1. Roger J Davis, University of Massachusetts Medical School, United States

Publication history

  1. Received: October 8, 2016
  2. Accepted: March 9, 2017
  3. Accepted Manuscript published: March 13, 2017 (version 1)
  4. Version of Record published: April 11, 2017 (version 2)

Copyright

© 2017, Jeannot 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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