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

Tania M. Puvirajesinghe, François Bertucci, Ashish Jain, Pierluigi Scerbo, Edwige Belotti, Stéphane Audebert, Michael Sebbagh, Marc Lopez, Andreas Brech, Pascal Finetti, Emmanuelle Charafe-Jauffret, Max Chaffanet, Rémy Castellano, Audrey Restouin, Sylvie Marchetto, Yves Collette, Anthony Gonçalvès, Ian Macara, Daniel Birnbaum, Laurent Kodjabachian, Terje Johansen and Jean-Paul Borg ()
Additional contact information
Tania M. Puvirajesinghe: CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
François Bertucci: Institut Paoli-Calmettes
Ashish Jain: Molecular Cancer Research Group, University of Tromsø—The Arctic University of Norway
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’
Stéphane Audebert: Institut Paoli-Calmettes
Michael Sebbagh: CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
Marc Lopez: Institut Paoli-Calmettes
Andreas Brech: Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital
Pascal Finetti: Institut Paoli-Calmettes
Emmanuelle Charafe-Jauffret: Institut Paoli-Calmettes
Max Chaffanet: Institut Paoli-Calmettes
Rémy Castellano: Institut Paoli-Calmettes
Audrey Restouin: Institut Paoli-Calmettes
Sylvie Marchetto: CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
Yves Collette: Institut Paoli-Calmettes
Anthony Gonçalvès: CRCM, Cell Polarity, Cell signalling and Cancer ‘Equipe labellisée Ligue Contre le Cancer’
Ian Macara: University of Virginia School of Medicine
Daniel Birnbaum: Institut Paoli-Calmettes
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’

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10318

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