Rab1A promotes cancer metastasis and radioresistance through activating GSK-3ß/Wnt/ß-catenin signaling in nasopharyngeal carcinoma.
Aging (Albany NY)
; 12(20): 20380-20395, 2020 10 17.
Article
em En
| MEDLINE
| ID: mdl-33068388
ABSTRACT
Many articles have reported that Rab1A was overexpressed in a variety of human cancers and involved in tumor progression and metastasis. However, the biological function and molecular mechanism of Rab1A in nasopharyngeal carcinoma (NPC) remained unknown until now. Here we found that Rab1A overexpression is a common event and was positively associated with distant metastasis and poor prognosis of NPC patients. Functionally, Rab1A depletion inhibited the migration and EMT phenotype of NPC cells, whereas Rab1A overexpression led to the opposite effect. Furthermore, we reveal an important role for Rab1A protein in the induction of radioresistance via regulating homologous recombination (HR) signaling pathway. Mechanistically, Rab1A activated Wnt/ß-catenin signaling by inhibiting the activity of GSK-3ß via phosphorylation at Ser9. Then Wnt/ß-catenin signaling induced NPC cells radioresistance and metastasis through nuclear translocation of ß-catenin and transcription upregulation of HR pathway-related and EMT-related genes expression. In general, this study shows that Rab1A may serve as a potential biomarker for predicting prognosis in NPC patients. Targeting Rab1A and Wnt/ß-catenin signaling may hold promise to overcome NPC radioresistance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tolerância a Radiação
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Movimento Celular
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Neoplasias Nasofaríngeas
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Proteínas rab1 de Ligação ao GTP
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Beta Catenina
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Via de Sinalização Wnt
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Glicogênio Sintase Quinase 3 beta
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Carcinoma Nasofaríngeo
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Aging (Albany NY)
Ano de publicação:
2020
Tipo de documento:
Article