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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Nature Publishing Group
2021
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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) |
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Medicine R Biology (General) QH301-705.5 |
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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 |
work_keys_str_mv |
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