EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer.
Biomolecules
; 11(4)2021 04 18.
Article
em En
| MEDLINE
| ID: mdl-33919657
ABSTRACT
EPHA3, a member of the EPH family, is overexpressed in various cancers. We demonstrated previously that EPHA3 is associated with radiation resistance in head and neck cancer via the PTEN/Akt/EMT pathway; the inhibition of EPHA3 significantly enhances the efficacy of radiotherapy in vitro and in vivo. In this study, we investigated the mechanisms of PTEN regulation through EPHA3-related signaling. Increased DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2) levels, along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, correlated with decreased levels of PTEN in radioresistant head and neck cancer cells. Furthermore, PTEN is regulated in two ways DNMT1-mediated DNA methylation, and EZH2-mediated histone methylation through EPHA3/C-myc signaling. Our results suggest that EPHA3 could display a novel regulatory mechanism for the epigenetic regulation of PTEN in radioresistant head and neck cancer cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tolerância a Radiação
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Receptor EphA3
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PTEN Fosfo-Hidrolase
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Repressão Epigenética
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Neoplasias de Cabeça e Pescoço
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article