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XB-ART-52202
Nat Commun April 11, 2016; 7 10318.

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

Puvirajesinghe TM , Bertucci F , Jain A , Scerbo P , Belotti E , Audebert S , Sebbagh M , Lopez M , Brech A , Finetti P , Charafe-Jauffret E , Chaffanet M , Castellano R , Restouin A , Marchetto S , Collette Y , Gonçalvès A , Macara I , Birnbaum D , Kodjabachian L , Johansen T , Borg JP .


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.

PubMed ID: 26754771
PMC ID: PMC4729931
Article link: Nat Commun


Species referenced: Xenopus
Genes referenced: pcdh8 sox2 sqstm1 tbxt vangl2 wnt5a
GO keywords: autophagy [+]
Morpholinos: sqstm1 MO1 sqstm1 MO2 vangl2 MO2

Disease Ontology terms: breast cancer
OMIMs: BREAST CANCER
Phenotypes: Xla Wt + DN-SQSTM1 (Fig. 6 f ) [+]

Article Images: [+] show captions
References [+] :
Adélaïde, Integrated profiling of basal and luminal breast cancers. 2007, Pubmed