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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 
Admission datedc.date.accessioned2019-10-14T15:41:07Z
Available datedc.date.available2019-10-14T15:41:07Z
Publication datedc.date.issued2019
Cita de ítemdc.identifier.citationOral Oncology 94 (2019) 58–67
Identifierdc.identifier.issn18790593
Identifierdc.identifier.issn13688375
Identifierdc.identifier.other10.1016/j.oraloncology.2019.05.010
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/171535
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.
Lenguagedc.language.isoen
Publisherdc.publisherElsevier
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
Sourcedc.sourceOral Oncology
Keywordsdc.subjectCell signaling
Keywordsdc.subjectKeratinocyte
Keywordsdc.subjectOral cancer
Keywordsdc.subjectOral dysplasia
Keywordsdc.subjectSurvivin
Keywordsdc.subjectWnt
Keywordsdc.subjectβ-Catenin
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
Catalogueruchile.catalogadorlaj
Indexationuchile.indexArtículo de publicación SCOPUS
uchile.cosechauchile.cosechaSI


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