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

Biomolecules

SeongWho Kim¹  HyoWon Chang²  SangYoon Kim²  JaeHee An³  Daseul Seong³  MyungWoul Han³  WonHyeok Lee³  ByungChul Kang³  SongHee Kim³  HeeJeong Cha⁴  HyoungUk Je⁵ 

[1] Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;Department of Otolaryngology, Asan medical center, University of Ulsan College of Medicine, Seoul 05505, Korea;Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea;Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea;Department of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea;

关键词: head and neck cancer;    radioresistance;    PTEN;    EPHA3;    C-myc;    DNMT1;   

DOI  :  10.3390/biom11040599

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown