Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response

Abstract Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism rem...

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Autores principales: Jiang He, Liyu Liu, Feiyu Tang, You Zhou, Huan Liu, Can Lu, Deyun Feng, Hong Zhu, Yitao Mao, Zhi Li, Lu Zhang, Yuemei Duan, Zhi Xiao, Musheng Zeng, Liang Weng, Lun-Quan Sun
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Lenguaje:EN
Publicado: Nature Publishing Group 2021
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Acceso en línea:https://doaj.org/article/37c8cc13b2fc461dbafdcb07de6276b4
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spelling oai:doaj.org-article:37c8cc13b2fc461dbafdcb07de6276b42021-11-28T12:08:41ZParadoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response10.1038/s41392-021-00787-x2059-3635https://doaj.org/article/37c8cc13b2fc461dbafdcb07de6276b42021-11-01T00:00:00Zhttps://doi.org/10.1038/s41392-021-00787-xhttps://doaj.org/toc/2059-3635Abstract Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism remains unclear. Here, we reported that the oncoproteins of DNA viruses, such as LMP1 of EBV and E7 of HPV, inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif. Inhibition of PERK led to increased level of reactive oxygen species (ROS) that promoted tumor and enhanced the efficacy of chemotherapy in vivo. Consistently, disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models. Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.Jiang HeLiyu LiuFeiyu TangYou ZhouHuan LiuCan LuDeyun FengHong ZhuYitao MaoZhi LiLu ZhangYuemei DuanZhi XiaoMusheng ZengLiang WengLun-Quan SunNature Publishing GrouparticleMedicineRBiology (General)QH301-705.5ENSignal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Biology (General)
QH301-705.5
spellingShingle Medicine
R
Biology (General)
QH301-705.5
Jiang He
Liyu Liu
Feiyu Tang
You Zhou
Huan Liu
Can Lu
Deyun Feng
Hong Zhu
Yitao Mao
Zhi Li
Lu Zhang
Yuemei Duan
Zhi Xiao
Musheng Zeng
Liang Weng
Lun-Quan Sun
Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
description Abstract Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism remains unclear. Here, we reported that the oncoproteins of DNA viruses, such as LMP1 of EBV and E7 of HPV, inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif. Inhibition of PERK led to increased level of reactive oxygen species (ROS) that promoted tumor and enhanced the efficacy of chemotherapy in vivo. Consistently, disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models. Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.
format article
author Jiang He
Liyu Liu
Feiyu Tang
You Zhou
Huan Liu
Can Lu
Deyun Feng
Hong Zhu
Yitao Mao
Zhi Li
Lu Zhang
Yuemei Duan
Zhi Xiao
Musheng Zeng
Liang Weng
Lun-Quan Sun
author_facet Jiang He
Liyu Liu
Feiyu Tang
You Zhou
Huan Liu
Can Lu
Deyun Feng
Hong Zhu
Yitao Mao
Zhi Li
Lu Zhang
Yuemei Duan
Zhi Xiao
Musheng Zeng
Liang Weng
Lun-Quan Sun
author_sort Jiang He
title Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
title_short Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
title_full Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
title_fullStr Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
title_full_unstemmed Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
title_sort paradoxical effects of dna tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/37c8cc13b2fc461dbafdcb07de6276b4
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