AEG-1/MTDH-activated autophagy enhances human malignant glioma susceptibility to TGF-ß1-triggered epithelial-mesenchymal transition.
Oncotarget
; 7(11): 13122-38, 2016 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-26909607
ABSTRACT
Autophagy is a tightly regulated process activated in response to metabolic stress and other microenvironmental changes. Astrocyte elevated gene 1 (AEG-1) reportedly induces protective autophagy. Our results indicate that AEG-1 also enhances the susceptibility of malignant glioma cells to TGF-ß1-triggered epithelial-mesenchymal transition (EMT) through induction of autophagy. TGF-ß1 induced autophagy and activated AEG-1 via Smad2/3 phosphorylation in malignant glioma cells. Also increased was oncogene cyclin D1 and EMT markers, which promoted tumor progression. Inhibition of autophagy using siRNA-BECN1 and siRNA-AEG-1 suppressed EMT. In tumor samples from patients with malignant glioma, immunohistochemical assays showed that expression levels of TGF-ß1, AEG-1, and markers of autophagy and EMT, all gradually increase with glioblastoma progression. In vivo siRNA-AEG-1 administration to rats implanted with C6 glioma cells inhibited tumor growth and increased the incidence of apoptosis among tumor cells. These findings shed light on the mechanisms underlying the invasiveness and progression of malignant gliomas.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Moléculas de Adesão Celular
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Fator de Crescimento Transformador beta1
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Transição Epitelial-Mesenquimal
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Glioma
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article