title: Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer.
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.
authors.affiliation: CRCM, Cell Polarity, Cell signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.|Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.
authors.forename: Tania M
authors.initials: TM
authors.lastname: Puvirajesinghe
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Molecular Cancer Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø 9037, Norway.|Department of Molecular Cell Biology, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Oslo N-0310, Norway.
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.affiliation: Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS UMR 7288, Marseille F-13288, France.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Scerbo
authors.affiliation: CRCM, Cell Polarity, Cell signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.|Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Belotti
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Marseille Proteomics Platform, Inserm, U1068, Marseille F-13009, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audebert
authors.affiliation: CRCM, Cell Polarity, Cell signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.|Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Sebbagh
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
authors.forename: Marc
authors.identifier: http://orcid.org/0000-0002-6573-633X
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Department of Molecular Cell Biology, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Oslo N-0310, Norway.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brech
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, TrGET Platform, Inserm, U1068, Marseille F-13009, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Castellano
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, TrGET Platform, Inserm, U1068, Marseille F-13009, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Restouin
authors.affiliation: CRCM, Cell Polarity, Cell signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.|Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Marchetto
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, TrGET Platform, Inserm, U1068, Marseille F-13009, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Collette
authors.affiliation: CRCM, Cell Polarity, Cell signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.|Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Marseille Proteomics Platform, Inserm, U1068, Marseille F-13009, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalvès
authors.affiliation: Department of Microbiology, University of Virginia School of Medicine, Charlottesville, Virginia, Tennessee 37240-7935, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Macara
authors.affiliation: Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.affiliation: Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS UMR 7288, Marseille F-13288, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjabachian
authors.affiliation: Molecular Cancer Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø 9037, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
authors.affiliation: CRCM, Cell Polarity, Cell signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.|Institut Paoli-Calmettes, Marseille F-13009, France.|Aix-Marseille Université, Marseille F-13284, France.|CNRS, UMR725, Marseille F-13009, France.|CRCM, Marseille Proteomics Platform, Inserm, U1068, Marseille F-13009, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity; D049109:Cell Proliferation / Q000235:genetics; D056915:DNA Copy Number Variations; D004625:Embryo, Nonmammalian; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D060449:Wnt Signaling Pathway / Q000235:genetics*; D014981:Xenopus
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C468513:VANGL2 protein, human