Wnt/β-Catenin Pathway

Abstract

Wnts are secreted glycoproteins that act as ligands to stimulate receptor-mediated signal transduction pathways in both vertebrates and invertebrates. Activation of Wnt pathways can modulate cell proliferation, survival, cell behavior, and cell fate in both embryos and adults. The Wnt/β-catenin pathway is the best understood Wnt signaling pathway, and its core components are highly conserved during evolution, although tissue-specific or species-specific modifiers of the pathway are likely. In the absence of a Wnt signal, cytoplasmic β-catenin is phosphorylated and degraded in a complex of proteins. Wnt signaling through the Frizzled serpentine receptor and low-density lipoprotein receptor-related protein-5 or -6 (LRP5 or 6) coreceptors activates the cytoplasmic phosphoprotein Dishevelled, which blocks the degradation of β-catenin. As the amount of β-catenin rises, it accumulates in the nucleus, where it interacts with specific transcription factors, leading to regulation of target genes. Inappropriate activation of the pathway in response to mutations is linked to a wide range of cancers, including colorectal cancer and melanoma. The pathway is linked to bone density syndromes and to neurodegenerative diseases, and the pathway may also be involved in the retinal disease familial exudative vitreoretinopathy.