Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma  

作　　者：Jiajun Xie Zifeng Wang Wenjun Fan Youping Liu Fang Liu Xiangbo Wan Meiling Liu Xuan Wang Deshun Zeng Van Wang Bin He Min Yan Zijian Zhang Mengjuan Zhang Zhijie Hou Chunli Wang Zhijie Kang Wenfeng Fang Li Zhang Eric W-F Lam Xiang Guo Jinsong Yan Yixin Zeng Mingyuan Chen Quentin Liu 

机构地区：[1]Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy,Guangzhou,China [2]Institute of Cancer Stem Cell,Cancer Center,Dalian Medical University,Dalian,China [3]Department of Hematology,Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine,Liaoning Medical Center for Hematopoietic Stem Cell Transplantation,Dalian Key Laboratory of Hematology,Diamond Bay Institute of Hematology,The Affiliated Second Hospital of Dalian Medical University,Dalian,China [4]Department of Radiation Oncology,The Sixth Affiliated Hospital of Sun Yat-sen University,Guangzhou,China [5]Sun Yat-sen Institute of Hematology,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第10期3045-3061,共17页信号转导与靶向治疗（英文）

基　　金：supported by National Key R&D Program of China(2019YFA0110300,2017YFA0505600-04 to Q.L.);Innovative Research Team in University of Ministry of Education of China(IRT_17R15 to Q.L.);National Natural Science Foundation of China(81630005,81573025 to Q.L.,81773166 to Z.W.,81702683 to J.X.,81972594 to M.Y.,81402445 to C.W.,81502579 to Z.H.);Natural Science Foundation of Guangdong(2017A030313608 to Q.L,2018A0303130299,2020A1515010608 to M.Y.);the Science and Technology Planning Project of Guangzhou(201804020044 to Q.L.);the Key Project of Liaoning Natural Science Funding of China(201702031 to Q.L.);Fundamental Research Funds for the Central Universities(I9ykpy187 to M.Y.).EW-FL's work is supported by MRC(MR/N012097/1);CRUK(Al 2011);Breast Cancer Now(2012MayPR070,2012NovPhD016);the Cancer Research UK Imperial Centre,Imperial ECMC,and NIHR Imperial BRC.

摘　　要：Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging.Nasopharyngeal carci noma(NPC)is a distinctive cancer with poor differe ntiatio n and high prevalenee of Epstein-Barr virus(EBV)infection.Here,we show that the expressi on of EBV latent protein LMP1 in duces dediffere ntiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA.Mechanistically,LMP1 upregulates STAT5A and recruits HDAC 1/2 to the CEBPA locus to reduce its histone acetylation.HDAC inhibition restored CEBPA expression,reversing cellular dedifferentiation and stem-like status in mouse xeno graft models.These fin dings provide a novel mecha nistic epigenetic-based in sight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

关 键 词：LMP1 cancer PLASTICITY 

分 类 号：R739.63[医药卫生—肿瘤]