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

作　　者：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 

机构地区：[1]Department of Oncology,Xiangya Cancer Center,Xiangya Hospital,Central South University,Changsha 410008,China [2]Key Laboratory of Molecular Radiation Oncology Hunan Province,Changsha 410008,China [3]Department of Pathology,Tongji Medical College Union Hospital,Huazhong University of Science and Technology,Wuhan 430022,China [4]Department of Pathology,Xiangya Hospital,Central South University,Changsha 410078,China [5]Department of Radiology,Xiangya Hospital,Central South University,Changsha 410078,China [6]Institute of Gerontological Cancer Research,National Clinical Research Center for Gerontology,Changsha 410008,China [7]Department of Breast Surgery,Xiangya Hospital,Central South University,Changsha 410078,China [8]State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-Sen University Cancer Center,Guangzhou 510060,China [9]Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer,Changsha 410008,China [10]Center for Molecular Imaging of Central South University,Xiangya Hospital,Changsha 410008,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第12期3767-3782,共16页信号转导与靶向治疗（英文）

基　　金：This work was funded by the following grants and associations:National Natural Science Foundations of China(81530084 and 81702721);Hunan province natural science funds for Yong scholars(2018JJ3816).

摘　　要：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.

关 键 词：CHEMOTHERAPY EPITHELIUM CERVICAL 

分 类 号：R73[医药卫生—肿瘤]