Epigenetic downregulation of STAT6 increases HIF-1α expression via mTOR/S6K/S6, leading to enhanced hypoxic viability of glioma cells.
Acta Neuropathol Commun
; 7(1): 149, 2019 09 17.
Article
en En
| MEDLINE
| ID: mdl-31530290
ABSTRACT
Multifunctional signal transducer and activator of transcription (STAT) proteins play important roles in cancer. Here, we have shown that STAT6 is epigenetically silenced in some cases of malignant glioblastoma, which facilitates cancer cell survival in a hypoxic microenvironment. This downregulation results from hypermethylation of CpG islands within the STAT6 promoter by DNA methyltransferases. STAT6 interacts with Rheb under hypoxia and inhibits mTOR/S6K/S6 signaling, in turn, inducing increased HIF-1α translation. STAT6 silencing and consequent tumor-promoting effects are additionally observed in glioma stem-like cells (GSC). Despite recent advances in cancer treatment, survival rates have shown little improvement. This is particularly true in the case of glioma, where multimodal treatment and precision medicine is needed. Our study supports the application of epigenetic restoration of STAT6 with the aid of DNA methyltransferase inhibitors, such as 5-aza-2-deoxycytidine, for treatment of STAT6-silenced gliomas.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Neoplasias Encefálicas
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Regulación Neoplásica de la Expresión Génica
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Glioblastoma
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Epigénesis Genética
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Factor de Transcripción STAT6
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Subunidad alfa del Factor 1 Inducible por Hipoxia
Límite:
Humans
Idioma:
En
Revista:
Acta Neuropathol Commun
Año:
2019
Tipo del documento:
Article
País de afiliación:
Corea del Sur