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Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2–JNK signalling in breast cancer

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  • Tania M. Puvirajesinghe

    (CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
    Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725)

  • François Bertucci

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, Molecular Oncology ‘Equipe labellisée Ligue Contre le Cancer’)

  • Ashish Jain

    (Molecular Cancer Research Group, University of Tromsø—The Arctic University of Norway
    Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital)

  • Pierluigi Scerbo

    (Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS UMR 7288)

  • Edwige Belotti

    (CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
    Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725)

  • Stéphane Audebert

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, Marseille Proteomics Platform)

  • Michael Sebbagh

    (CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
    Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725)

  • Marc Lopez

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, Molecular Oncology ‘Equipe labellisée Ligue Contre le Cancer’)

  • Andreas Brech

    (Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital)

  • Pascal Finetti

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, Molecular Oncology ‘Equipe labellisée Ligue Contre le Cancer’)

  • Emmanuelle Charafe-Jauffret

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, Molecular Oncology ‘Equipe labellisée Ligue Contre le Cancer’)

  • Max Chaffanet

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, Molecular Oncology ‘Equipe labellisée Ligue Contre le Cancer’)

  • Rémy Castellano

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, TrGET Platform)

  • Audrey Restouin

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, TrGET Platform)

  • Sylvie Marchetto

    (CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
    Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725)

  • Yves Collette

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, TrGET Platform)

  • Anthony Gonçalvès

    (CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
    Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725)

  • Ian Macara

    (University of Virginia School of Medicine)

  • Daniel Birnbaum

    (Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725
    CRCM, Molecular Oncology ‘Equipe labellisée Ligue Contre le Cancer’)

  • Laurent Kodjabachian

    (Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS UMR 7288)

  • Terje Johansen

    (Molecular Cancer Research Group, University of Tromsø—The Arctic University of Norway)

  • Jean-Paul Borg

    (CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
    Institut Paoli-Calmettes
    Aix-Marseille Université
    CNRS, UMR725)

Abstract

The non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway plays a crucial role in embryonic development. Recent work has linked defects of this pathway to breast cancer aggressiveness and proposed Wnt/PCP signalling as a therapeutic target. Here we show that the archetypal Wnt/PCP protein VANGL2 is overexpressed in basal breast cancers, associated with poor prognosis and implicated in tumour growth. We identify the scaffold p62/SQSTM1 protein as a novel VANGL2-binding partner and show its key role in an evolutionarily conserved VANGL2–p62/SQSTM1–JNK pathway. This proliferative signalling cascade is upregulated in breast cancer patients with shorter survival and can be inactivated in patient-derived xenograft cells by inhibition of the JNK pathway or by disruption of the VANGL2–p62/SQSTM1 interaction. VANGL2–JNK signalling is thus a potential target for breast cancer therapy.

Suggested Citation

  • Tania M. Puvirajesinghe & François Bertucci & Ashish Jain & Pierluigi Scerbo & Edwige Belotti & Stéphane Audebert & Michael Sebbagh & Marc Lopez & Andreas Brech & Pascal Finetti & Emmanuelle Charafe-J, 2016. "Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2–JNK signalling in breast cancer," Nature Communications, Nature, vol. 7(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10318
    DOI: 10.1038/ncomms10318
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