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MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment

文献类型：期刊论文

作者Wang, Bing1,2,4,5; Lim, Chuan-Bian4; Yan, Jiawei3,4; Li, Lizhen4; Wang, Jufang2,5; Little, John B.4; Yuan, Zhi-Min4
刊名JOURNAL OF MOLECULAR CELL BIOLOGY
出版日期2020-09-01
卷号12期号:9页码:713-722
关键词p53 MDMX tumor microenvironment immune cell infiltration macrophage polarization
ISSN号1674-2788
DOI10.1093/jmcb/mjaa038
通讯作者Yuan, Zhi-Min(zyuan@hsph.harvard.edu)
英文摘要A role of tumor-suppressive activity of p53 in the tumor microenvironment (TME) has been implicated but remains fairly understudied. To address this knowledge gap, we leveraged our Mdmx(S314A) mice as recipients to investigate how implanted tumor cells incapacitate host p53 creating a conducive TME for tumor progression. We found that tumor cell-associated stress induced p53 downregulation in peritumor cells via an MDMX-Ser314 phosphorylation-dependent manner. As a result, an immunosuppressive TME was developed, as reflected by diminished immune cell infiltration into tumors and compromised macrophage M1 polarization. Remarkably, ablation of MDMX-Ser314 phosphorylation attenuated p53 decline in peritumor cells, which was associated with mitigation of immunosuppression and significant tumor growth delay. Our data collectively uncover a novel role of p53 in regulating the tumor immune microenvironment, suggesting that p53 restoration in the TME can be exploited as a potential strategy of anticancer therapy.
WOS关键词SUPPRESSES P53 ; PROGRESSION ; COMPLEX ; TRP53
资助项目Morningside Foundation ; National Cancer Institute at the National Institutes of Health[R01CA233558] ; National Cancer Institute at the National Institutes of Health[R01CA167814] ; National Cancer Institute at the National Institutes of Health[R01CA125144]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000605614800005
出版者OXFORD UNIV PRESS
资助机构Morningside Foundation ; National Cancer Institute at the National Institutes of Health
源URL[http://119.78.100.186/handle/113462/138172]  
专题中国科学院近代物理研究所
通讯作者Yuan, Zhi-Min
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Chinese Acad Sci, Key Lab Space Radiobiol Gansu Prov, Inst Modern Phys, Lanzhou, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
4.Harvard TH Chan Sch Publ Hlth, John B Little Ctr Radiat Sci, Boston, MA 02115 USA
5.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Inst Modern Phys, Lanzhou, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Bing,Lim, Chuan-Bian,Yan, Jiawei,et al. MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2020,12(9):713-722.
APA Wang, Bing.,Lim, Chuan-Bian.,Yan, Jiawei.,Li, Lizhen.,Wang, Jufang.,...&Yuan, Zhi-Min.(2020).MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment.JOURNAL OF MOLECULAR CELL BIOLOGY,12(9),713-722.
MLA Wang, Bing,et al."MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment".JOURNAL OF MOLECULAR CELL BIOLOGY 12.9(2020):713-722.

入库方式： OAI收割

来源：近代物理研究所

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