Inhibition of PORCN Blocks Wnt Signaling to Attenuate Progression of Oral Carcinogenesis

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dc.contributor.authorPena-Oyarzun, Daniel
dc.contributor.authorFlores, Tania
dc.contributor.authorTorres, Vicente A.
dc.contributor.authorQuest, Andrew F. G.
dc.contributor.authorLobos-Gonzalez, Lorena
dc.contributor.authorKretschmar, Catalina
dc.contributor.authorContreras, Pamela
dc.contributor.authorMaturana-Ramirez, Andrea
dc.contributor.authorCriollo, Alfredo
dc.contributor.authorReyes, Montserrat
dc.date.accessioned2025-01-20T16:08:02Z
dc.date.available2025-01-20T16:08:02Z
dc.date.issued2024
dc.description.abstractPurpose: Oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, referred to as oral dysplasia. We recently reported that oral dysplasia is associated with aberrant activation of the Wnt/beta-catenin pathway, due to overexpression of Wnt ligands in a Porcupine (PORCN)-dependent manner. Pharmacologic inhibition of PORCN precludes Wnt secretion and has been proposed as a potential therapeutic approach to treat established cancers. Nevertheless, there are no studies that explore the effects of PORCN inhibition at the different stages of oral carcinogenesis.
dc.description.abstractExperimental Design: We performed a model of tobacco-induced oral cancer in vitro, where dysplastic oral keratinocytes (DOK) were transformed into oral carcinoma cells (DOK-TC), and assessed the effects of inhibiting PORCN with the C59 inhibitor. Similarly, an in vivo model of oral carcinogenesis and ex vivo samples derived from patients diagnosed with oral dysplasia and OSCC were treated with C59.
dc.description.abstractResults: Both in vitro and ex vivo oral carcinogenesis approaches revealed decreased levels of nuclear beta-catenin and Wnt3a, as observed by immunofluorescence and IHC analyses. Consistently, reduced protein and mRNA levels of survivin were observed after treatment with C59. Functionally, treatment with C59 in vitro resulted in diminished cell migration, viability, and invasion. Finally, by using an in vivo model of oral carcinogenesis, we found that treatment with C59 prevented the development of OSCC by reducing the size and number of oral tumor lesions.
dc.description.abstractConclusions: The inhibition of Wnt ligand secretion with C59 represents a feasible treatment to prevent the progression of early oral lesions toward OSCC.
dc.fuente.origenWOS
dc.identifier.doi10.1158/1078-0432.CCR-23-0318
dc.identifier.eissn1557-3265
dc.identifier.issn1078-0432
dc.identifier.urihttps://doi.org/10.1158/1078-0432.CCR-23-0318
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90044
dc.identifier.wosidWOS:001313528800023
dc.issue.numero1
dc.language.isoen
dc.pagina.final223
dc.pagina.inicio209
dc.revistaClinical cancer research
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInhibition of PORCN Blocks Wnt Signaling to Attenuate Progression of Oral Carcinogenesis
dc.typeartículo
dc.volumen30
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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