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A caveolin-dependent and PI3K/AKT-independent role of PTEN in β-catenin transcriptional activity

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  • Alejandro Conde-Perez

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Gwendoline Gros

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Christine Longvert

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Malin Pedersen

    (Targeted Therapy Team, The Institute of Cancer Research)

  • Valérie Petit

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Zackie Aktary

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Amaya Viros

    (Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester)

  • Franck Gesbert

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Véronique Delmas

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Florian Rambow

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Boris C. Bastian

    (University of California San Francisco)

  • Andrew D. Campbell

    (The Beatson Institute for Cancer Research)

  • Sophie Colombo

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Isabel Puig

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

  • Alfonso Bellacosa

    (Fox Chase Cancer Center)

  • Owen Sansom

    (The Beatson Institute for Cancer Research)

  • Richard Marais

    (Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester)

  • Leon C. L. T. Van Kempen

    (Radboud University Nijmegen Medical Centre
    Jewish General Hospital, Lady Davis Institute for Medical Research
    McGill University)

  • Lionel Larue

    (Normal and Pathological Development of Melanocytes, Institut Curie
    CNRS, UMR3347 Bat. 110
    INSERM U1021
    Equipe labellisée-Ligue Nationale contre le Cancer)

Abstract

Loss of the tumour suppressor PTEN is frequent in human melanoma, results in MAPK activation, suppresses senescence and mediates metastatic behaviour. How PTEN loss mediates these effects is unknown. Here we show that loss of PTEN in epithelial and melanocytic cell lines induces the nuclear localization and transcriptional activation of β-catenin independent of the PI3K–AKT–GSK3β axis. The absence of PTEN leads to caveolin-1 (CAV1)-dependent β-catenin transcriptional modulation in vitro, cooperates with NRASQ61K to initiate melanomagenesis in vivo and induces efficient metastasis formation associated with E-cadherin internalization. The CAV1-β–catenin axis is mediated by a feedback loop in which β-catenin represses transcription of miR-199a-5p and miR-203, which suppress the levels of CAV1 mRNA in melanoma cells. These data reveal a mechanism by which loss of PTEN increases CAV1-mediated dissociation of β-catenin from membranous E-cadherin, which may promote senescence bypass and metastasis.

Suggested Citation

  • Alejandro Conde-Perez & Gwendoline Gros & Christine Longvert & Malin Pedersen & Valérie Petit & Zackie Aktary & Amaya Viros & Franck Gesbert & Véronique Delmas & Florian Rambow & Boris C. Bastian & An, 2015. "A caveolin-dependent and PI3K/AKT-independent role of PTEN in β-catenin transcriptional activity," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9093
    DOI: 10.1038/ncomms9093
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