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Nuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia

Authordc.contributor.authorReyes Rojas, Montserrat 
Authordc.contributor.authorPeña Oyarzún, Daniel 
Authordc.contributor.authorMaturana Ramírez, Andrea 
Authordc.contributor.authorTorres Gómez, Vicente 
Cita de ítemdc.identifier.citationOral Oncology 94 (2019) 58–67
Abstractdc.description.abstractObjectives: To evaluate the localization of β-catenin in oral dysplastic cells, the expression of target genes upregulated in oral dysplasia, and the role of Wnt ligands in these events. Materials and methods: Subcellular localization of total and non-phosphorylated (transcriptionally active) β- catenin was evaluated by immunofluorescence and biochemical fractionation in dysplastic oral keratinocytes (DOK), non-dysplastic oral keratinocytes (OKF6), oral squamous carcinoma cells (CAL27) and primary oral keratinocytes. Tcf/Lef-dependent transcription was measured by luciferase reporter assays. Expression of target genes, survivin and cyclin D1, was evaluated by RT-qPCR and Western blotting. Wnt secretion was inhibited with the inhibitor of porcupine, C59. Wnt3a and β-catenin were evaluated in biopsies by tissue immunofluorescence. Results: Immunofluorescence and fractionation experiments showed augmented nuclear β-catenin (total and transcriptionally active) in DOK, when compared with OKF6 and CAL27 cells. Intriguingly, conditioned medium from DOK promoted nuclear accumulation of β-catenin and Tcf/Lef-dependent transcription in OKF6 and primary oral keratinocytes, suggesting the participation of secreted factors. Treatment of DOK with C59 decreased Wnt3a secretion, nuclear β-catenin and the expression of survivin and cyclin D1 at both mRNA and protein levels. Accordingly, DOK secreted higher Wnt3a levels than OKF6, and inhibition of Wnt3a secretion prevented DOK-induced Tcf/Lef-dependent transcription in OKF6. These observations were confirmed in clinical samples, since tissue immunofluorescence analysis showed simultaneous expression of Wnt3a and nuclear β-catenin in oral dysplasia, but not in healthy mucosa biopsies. Conclusion: These data indicate that secretion of Wnt ligands is critical for β-catenin nuclear localization and expression of target genes in oral dysplasia.
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
Link to Licensedc.rights.uri
Sourcedc.sourceOral Oncology
Keywordsdc.subjectCell signaling
Keywordsdc.subjectOral cancer
Keywordsdc.subjectOral dysplasia
Títulodc.titleNuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia
Document typedc.typeArtículo de revista
Indexationuchile.indexArtículo de publicación SCOPUS

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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile