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Article Dans Une Revue Nature Communications Année : 2016

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

Pascal Finetti
Max Chaffanet
Daniel Birnbaum
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Résumé

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.
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Dates et versions

hal-01447570 , version 1 (27-01-2017)

Identifiants

Citer

Tania M. Puvirajesinghe, François Bertucci, Ashish Jain, Pierluigi Scerbo, Edwige Belotti, et al.. Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2–JNK signalling in breast cancer. Nature Communications, 2016, 7, pp.10318. ⟨10.1038/ncomms10318⟩. ⟨hal-01447570⟩
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