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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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/4/599 |
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| author | Song-Hee Kim Byung-Chul Kang Daseul Seong Won-Hyeok Lee Jae-Hee An Hyoung-Uk Je Hee-Jeong Cha Hyo-Won Chang Sang-Yoon Kim Seong-Who Kim Myung-Woul Han |
| author_facet | Song-Hee Kim Byung-Chul Kang Daseul Seong Won-Hyeok Lee Jae-Hee An Hyoung-Uk Je Hee-Jeong Cha Hyo-Won Chang Sang-Yoon Kim Seong-Who Kim Myung-Woul Han |
| author_sort | Song-Hee Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:12:56Z |
| format | Article |
| id | doaj.art-d35491c7cd4a49b6a1e246e1abf306dd |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T12:12:56Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d35491c7cd4a49b6a1e246e1abf306dd2023-11-21T16:06:51ZengMDPI AGBiomolecules2218-273X2021-04-0111459910.3390/biom11040599EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck CancerSong-Hee Kim0Byung-Chul Kang1Daseul Seong2Won-Hyeok Lee3Jae-Hee An4Hyoung-Uk Je5Hee-Jeong Cha6Hyo-Won Chang7Sang-Yoon Kim8Seong-Who Kim9Myung-Woul Han10Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaDepartment of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaDepartment of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaDepartment of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaDepartment of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaDepartment of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaDepartment of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaDepartment of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, KoreaEPHA3, 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.https://www.mdpi.com/2218-273X/11/4/599head and neck cancerradioresistancePTENEPHA3C-mycDNMT1 |
| spellingShingle | Song-Hee Kim Byung-Chul Kang Daseul Seong Won-Hyeok Lee Jae-Hee An Hyoung-Uk Je Hee-Jeong Cha Hyo-Won Chang Sang-Yoon Kim Seong-Who Kim Myung-Woul Han EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer Biomolecules head and neck cancer radioresistance PTEN EPHA3 C-myc DNMT1 |
| title | EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer |
| title_full | EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer |
| title_fullStr | EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer |
| title_full_unstemmed | EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer |
| title_short | EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer |
| title_sort | epha3 contributes to epigenetic suppression of pten in radioresistant head and neck cancer |
| topic | head and neck cancer radioresistance PTEN EPHA3 C-myc DNMT1 |
| url | https://www.mdpi.com/2218-273X/11/4/599 |
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