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- W2034792192 endingPage "e23899" @default.
- W2034792192 startingPage "e23899" @default.
- W2034792192 abstract "The Wnt/β-catenin signalling pathway shares a key component, β-catenin, with the cadherin-based adhesion system. The signalling function of β-catenin is conferred by a soluble cytoplasmic pool that is unstable in the absence of a Wnt signal, whilst the adhesion function is based on a cadherin-bound, stable pool at the membrane. The cadherin complex is dynamic, allowing for cell-cell rearrangements such as epithelial-mesenchymal transition (EMT), where the complex turns over through internalisation. Potential interplay between the two pools remains poorly understood, but cadherins are generally considered negative regulators of Wnt signalling because they sequester cytoplasmic β-catenin. Here we explore how cellular changes at EMT affect the signalling capacity of β-catenin using two models of EMT: hepatocyte growth factor (HGF) treatment of MDCK cells, and gastrulation in embryonic development. We show that EMT not only provides a pool of signalling-competent β-catenin following internalisation of cadherin, but also significantly facilitates activation of the Wnt pathway in response to both Wnt signals and exogenous β-catenin. We further demonstrate that availability of β-catenin in the cytoplasm does not necessarily correlate with Wnt/β-catenin pathway activity, since blocking endocytosis or depleting endogenous cadherin abolishes pathway activation despite the presence of β-catenin in the cytoplasm. Lastly we present data suggesting that cadherins are required for augmented activation of the Wnt/β-catenin pathway in vivo. This suggests that cadherins play a crucial role in β-catenin-dependent transcription." @default.
- W2034792192 created "2016-06-24" @default.
- W2034792192 creator A5049133868 @default.
- W2034792192 creator A5057997163 @default.
- W2034792192 creator A5061761252 @default.
- W2034792192 creator A5081294430 @default.
- W2034792192 date "2011-08-31" @default.
- W2034792192 modified "2023-10-04" @default.
- W2034792192 title "A Positive Role of Cadherin in Wnt/β-Catenin Signalling during Epithelial-Mesenchymal Transition" @default.
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- W2034792192 doi "https://doi.org/10.1371/journal.pone.0023899" @default.
- W2034792192 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3166074" @default.
- W2034792192 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21909376" @default.
- W2034792192 hasPublicationYear "2011" @default.
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