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Nat Commun. 2016 Jan 12;7:10318. doi: 10.1038/ncomms10318.

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

Puvirajesinghe TM1,2,3,4, Bertucci F2,3,4,5, Jain A6,7, Scerbo P8, Belotti E1,2,3,4, Audebert S2,3,4,9, Sebbagh M1,2,3,4, Lopez M2,3,4,5, Brech A7, Finetti P2,3,4,5, Charafe-Jauffret E2,3,4,5, Chaffanet M2,3,4,5, Castellano R2,3,4,10, Restouin A2,3,4,10, Marchetto S1,2,3,4, Collette Y2,3,4,10, Gonçalvès A1,2,3,4,9, Macara I11, Birnbaum D2,3,4,5, Kodjabachian L8, Johansen T6, Borg JP1,2,3,4,9.

Author information

1
CRCM, Cell Polarity, Cell signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
2
Institut Paoli-Calmettes, Marseille F-13009, France.
3
Aix-Marseille Université, Marseille F-13284, France.
4
CNRS, UMR725, Marseille F-13009, France.
5
CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Inserm, U1068, Marseille F-13009, France.
6
Molecular Cancer Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø 9037, Norway.
7
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.
8
Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS UMR 7288, Marseille F-13288, France.
9
CRCM, Marseille Proteomics Platform, Inserm, U1068, Marseille F-13009, France.
10
CRCM, TrGET Platform, Inserm, U1068, Marseille F-13009, France.
11
Department of Microbiology, University of Virginia School of Medicine, Charlottesville, Virginia, Tennessee 37240-7935, USA.

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.

PMID:
26754771
PMCID:
PMC4729931
DOI:
10.1038/ncomms10318
[Indexed for MEDLINE]
Free PMC Article

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