Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2–JNK signalling in breast cancer
- Resource Type
- Authors
- Michael Sebbagh; Anthony Gonçalves; Yves Collette; Ashish Jain; Max Chaffanet; Laurent Kodjabachian; Marc Lopez; Andreas Brech; Sylvie Marchetto; Jean-Paul Borg; Audrey Restouin; Pierluigi Scerbo; Terje Johansen; Daniel Birnbaum; Stéphane Audebert; Pascal Finetti; Edwige Belotti; Tania M. Puvirajesinghe; Emmanuelle Charafe-Jauffret; François Bertucci; Rémy Castellano; Ian G. Macara
- Source
- Nature Communications
Nature Communications, 2016, 7, pp.10318. ⟨10.1038/ncomms10318⟩
Nature Communications, Vol 7, Iss 1, Pp 1-15 (2016)
Nature Communications, Nature Publishing Group, 2016, 7, pp.10318. ⟨10.1038/ncomms10318⟩
- Subject
- 0301 basic medicine
Embryo, Nonmammalian
Xenopus
General Physics and Astronomy
[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Mass Spectrometry
Mice
Cell Movement
Cell polarity
Sequestosome-1 Protein
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
skin and connective tissue diseases
VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical molecular biology: 711
Wnt Signaling Pathway
[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Multidisciplinary
Carcinoma, Ductal, Breast
Wnt signaling pathway
Intracellular Signaling Peptides and Proteins
Signal transducing adaptor protein
LRP6
Cell Polarity
[SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis
LRP5
Middle Aged
Prognosis
3. Good health
Cell biology
Female
Cell Migration Assays
DNA Copy Number Variations
MAP Kinase Signaling System
Science
Blotting, Western
Breast Neoplasms
Biology
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Breast cancer
Downregulation and upregulation
Planar Polarity proteins
Breast cacner
Cell Line, Tumor
medicine
Animals
Humans
Immunoprecipitation
RNA, Messenger
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Adaptor Proteins, Signal Transducing
Cell Proliferation
Proportional Hazards Models
Cell growth
Membrane Proteins
General Chemistry
medicine.disease
Carcinoma, Lobular
Microscopy, Electron
030104 developmental biology
[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis
VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711
Neoplasm Transplantation
- Language
- English
- ISSN
- 2041-1723
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.
Defects in non-canonical Wnt/planar cell polarity signalling have recently been linked to breast cancer aggressiveness. Puvirajesinghe et al. identify VANGL2, p62/SQSTM1 and JNK as important players in this pathway which may be amenable to therapeutic intervention in breast cancer.