Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26754771.
- Also identified by DOI 10.1038/ncomms10318 and PMC identifier 4729931.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Breast Neoplasms
- Carcinoma, Ductal, Breast
- Carcinoma, Lobular
- Intracellular Signaling Peptides and Proteins
- MAP Kinase Signaling System
- Membrane Proteins
- RNA, Messenger
- Wnt Signaling Pathway