EBV LMP1-C terminal binding affibody molecule downregulates MEK/ERK/p90RSK pathway and inhibits the proliferation of nasopharyngeal carcinoma cells in mouse tumor xenograft models

doi:10.3389/fcimb.2022.1078504

科研成果详情

题名	EBV LMP1-C terminal binding affibody molecule downregulates MEK/ERK/p90RSK pathway and inhibits the proliferation of nasopharyngeal carcinoma cells in mouse tumor xenograft models
作者	Guo, Yanru; Kamara, Saidu; Zhang, Jing; Wen, He; Zheng, Maolin; Liu, Ying; Zhou, Luqi; Chen, Jun; Zhu, Shanli; Zhang, Lifang
发表日期	2023-01-04
发表期刊	FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	EBV LMP1 affibody molecules nasopharyngeal carcinoma targeted therapy
其他关键词	EPSTEIN-BARR-VIRUS ; MEMBRANE-PROTEIN 1 ; LATENT MEMBRANE-PROTEIN-1 ; EPITHELIAL-CELLS ; EXPRESSION ; TRANSFORMATION ; PATHOGENESIS
摘要	Nasopharyngeal carcinoma (NPC), is an Epstein-Barr virus (EBV) associated malignancy most common in Southern China and Southeast Asia. In southern China, it is one of the major causes of cancer-related death. Despite improvement in radiotherapy and chemotherapy techniques, locoregional recurrence and distant metastasis remains the major causes for failure of treatment in NPC patients. Therefore, finding new specific drug targets for treatment interventions are urgently needed. Here, we report three potential Z(LMP1-C) affibody molecules (Z(LMP1-C)15, Z(LMP1-C)114 and Z(LMP1-C)277) that showed specific binding interactions for recombinant and native EBV LMP1 as determined by epitope mapping, co-localization and co-immunoprecipitation assays. The Z(LMP1-C) affibody molecules exhibited high antitumor effects on EBV-positive NPC cell lines and displayed minimal cytotoxicity towards EBV-negative NPC cell line. Moreover, Z(LMP1-C)277 showed higher antitumor efficacy than Z(LMP1-C)15 and Z(LMP1-C)114 affibody molecules. The ability of Z(LMP1-C)277 decrease the phosphorylation levels of up-stream activator phospho-Raf-1((Ser338)), phospho-MEK1/2((Ser217/Ser221)), phospho-ERK1/2((Thr202/Thr204)), thereby leading to downstream suppression of phospho-p90RSK((Ser380)) and transcription factor c-Fos. Importantly, tumor growth was reduced in tumor-bearing mice treated with Z(LMP1-C)277 and caused no apparent toxicity. Taken together, our findings provide evidence that Z(LMP1-C)277 as a promising therapeutic agent in EBV-associated NPC.
资助项目	National Nature Science Foundation of China [81972550, 81372447]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	2235-2988
卷号	12
DOI	10.3389/fcimb.2022.1078504
页数	14
WOS类目	Immunology ; Microbiology
WOS研究方向	Immunology ; Microbiology
WOS记录号	WOS:000913496000001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	36683690
SCOPUSEID	2-s2.0-85146514580
通讯作者地址	[Zhang, Lifang]Institute of Molecular Virology and Immunology,Department of Microbiology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Microbiology;Immunology;Microbiology (medical);Infectious Diseases
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172079
专题	基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者	Zhang, Lifang
作者单位	Institute of Molecular Virology and Immunology,Department of Microbiology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,China
第一作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
第一作者的第一单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
推荐引用方式 GB/T 7714	Guo, Yanru,Kamara, Saidu,Zhang, Jing,et al. EBV LMP1-C terminal binding affibody molecule downregulates MEK/ERK/p90RSK pathway and inhibits the proliferation of nasopharyngeal carcinoma cells in mouse tumor xenograft models[J]. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,2023,12.
APA	Guo, Yanru., Kamara, Saidu., Zhang, Jing., Wen, He., Zheng, Maolin., ... & Zhang, Lifang. (2023). EBV LMP1-C terminal binding affibody molecule downregulates MEK/ERK/p90RSK pathway and inhibits the proliferation of nasopharyngeal carcinoma cells in mouse tumor xenograft models. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 12.
MLA	Guo, Yanru,et al."EBV LMP1-C terminal binding affibody molecule downregulates MEK/ERK/p90RSK pathway and inhibits the proliferation of nasopharyngeal carcinoma cells in mouse tumor xenograft models".FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY 12(2023).