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Annexin A8 (AnxA8), a calcium-dependent phospholipid-binding protein, and canonical Wnt signalling mechanisms have both been implicated in retinal pigment epithelial (RPE) cell differentiation. The aim here was to examine the possibility of cross-talk between AnxA8 and Wnt signalling, as both are down-regulated upon fenretinide (FR)-mediated RPE transdifferentiation. AnxA8 suppression in RPE cells via siRNA or administration of FR induced neuronal-like cell transdifferentiation and reduced expression of Wnt-related genes, as measured by real-time PCR and western blotting. AnxA8 gene expression, on the other hand, remained unaltered upon manipulating Wnt signalling, suggesting Wnt-related genes to be downstream effectors of AnxA8. Co-immunoprecipitation revealed an interaction between AnxA8 and \u03b2-catenin, which was reduced in the presence of activated TGF-\u03b21. TGF-\u03b21 signalling also reversed the AnxA8 loss-induced cell morphology changes, and induced \u03b2-catenin translocation and GSK-3\u03b2 phosphorylation in the absence of AnxA8. Ectopic over-expression of AnxA8 led to an increase in active \u03b2-catenin and GSK-3\u03b2 phosphorylation. These data demonstrate an important role for AnxA8 as a regulator of Wnt signalling and a determinant of RPE phenotype, with implications for regenerative medicine approaches that utilise stem cell-derived RPE cells to treat conditions such as age-related macular degeneration.<\/jats:p>","DOI":"10.1038\/s41598-020-58296-w","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T11:02:44Z","timestamp":1580122964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Annexin A8 regulates Wnt signaling to maintain the phenotypic plasticity of retinal pigment epithelial cells"],"prefix":"10.1038","volume":"10","author":[{"given":"Katharina","family":"Lueck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5469-0030","authenticated-orcid":false,"given":"Amanda-Jayne F.","family":"Carr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-2984","authenticated-orcid":false,"given":"John","family":"Greenwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E.","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,27]]},"reference":[{"key":"58296_CR1","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1167\/iovs.03-0943","volume":"45","author":"P Turowski","year":"2004","unstructured":"Turowski, P. et al. 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