EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer

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...

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Detalles Bibliográficos
Autores principales: Kim, Song-Hee, Kang, Byung-Chul, Seong, Daseul, Lee, Won-Hyeok, An, Jae-Hee, Je, Hyoung-Uk, Cha, Hee-Jeong, Chang, Hyo-Won, Kim, Sang-Yoon, Kim, Seong-Who, Han, Myung-Woul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073943/
https://www.ncbi.nlm.nih.gov/pubmed/33919657
http://dx.doi.org/10.3390/biom11040599
Descripción
Sumario: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.

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