气候变化领域集成服务门户(CCPortal): Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy

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DOI	10.1073/pnas.2018861118
	Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy
	Chen W.; Mou K.Y.; Solomon P.; Aggarwal R.; Leung K.K.; Wells J.A.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	MYC is a powerful transcription factor overexpressed in many human cancers including B cell and prostate cancers. Antibody therapeutics are exciting opportunities to attack cancers but require knowledge of surface proteins that change due to oncogene expression. To identify how MYC overexpression remodels the cell surface proteome in a cell autologous fashion and in different cell types, we investigated the impact of MYC overexpression on 800 surface proteins in three isogenic model cell lines either of B cell or prostate cell origin engineered to have high or low MYC levels. We found that MYC overexpression resulted in dramatic remodeling (both up- and down-regulation) of the cell surfaceome in a cell type-dependent fashion. We found systematic and large increases in distinct sets of >80 transporters including nucleoside transporters and nutrient transporters making cells more sensitive to toxic nucleoside analogs like cytarabine, commonly used for treating hematological cancers. Paradoxically, MYC overexpression also increased expression of surface proteins driving cell turnover such as TNFRSF10B, also known as death receptor 5, and immune cell attacking signals such as the natural killer cell activating ligand NCR3LG1, also known as B7-H6. We generated recombinant antibodies to these two targets and verified their up-regulation in MYC overexpression cell lines and showed they were sensitive to bispecific T cell engagers (BiTEs). Our studies demonstrate how MYC overexpression leads to dramatic bidirectional remodeling of the surfaceome in a cell type-dependent but functionally convergent fashion and identify surface targets or combinations thereof as possible candidates for cytotoxic metabolite or immunotherapy. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antibody; Glycoproteomics; MYC; Oncogenes; Surfaceome
语种	英语
scopus关键词	cell surface protein; cytarabine; death receptor 5; Myc protein; proteome; Article; B lymphocyte; cell engineering; cell metabolism; cell surface; controlled study; cytotoxicity; down regulation; gene; gene expression level; gene identification; gene overexpression; gene targeting; human; human cell; immunocompetent cell; immunotherapy; male; natural killer cell; NCR3LG1 gene; nucleoside transport; oncogene myc; priority journal; prostate cell; TNFRSF10B gene; upregulation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180846
作者单位	Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, United States; Department of Therapeutic Discovery, Amgen Research, Thousand Oaks, CA 91320, United States; Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan; Department of Medicine, University of California, San Francisco, CA 94158, United States; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, United States
推荐引用方式 GB/T 7714	Chen W.,Mou K.Y.,Solomon P.,et al. Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy[J],2021,118(4).
APA	Chen W.,Mou K.Y.,Solomon P.,Aggarwal R.,Leung K.K.,&Wells J.A..(2021).Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Chen W.,et al."Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).