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| Targeting IRF3 as a YAP agonist therapy against gastric cancer | |
| 2018-02 | |
| Source Publication | JOURNAL OF EXPERIMENTAL MEDICINE
 |
| ISSN | 0022-1007 |
| Volume | 215Issue:2Pages:699-718 |
| Status | 已发表 |
| DOI | 10.1084/jem.20171116 |
| Abstract | The Hippo pathway plays a vital role in tissue homeostasis and tumorigenesis. The transcription factor IRF3 is essential for innate antiviral immunity. In this study, we discovered IRF3 as an agonist of Yes-associated protein (YAP). The expression of IRF3 is positively correlated with that of YAP and its target genes in gastric cancer; the expression of both IRF3 and YAP is up-regulated and prognosticates patient survival. IRF3 interacts with both YAP and TEAD4 in the nucleus to enhance their interaction, promoting nuclear translocation and activation of YAP. IRF3 and YAP-TEAD4 are associated genome-wide to cobind and coregulate many target genes of the Hippo pathway. Overexpression of active IRF3 increased, but depletion of IRF3 reduced, the occupancy of YAP on the target genes. Knockdown or pharmacological targeting of IRF3 by Amlexanox, a drug used clinically for antiinflammatory treatment, inhibits gastric tumor growth in a YAP-dependent manner. Collectively, our study identifies IRF3 as a positive regulator for YAP, highlighting a new therapeutic target against YAP-driven cancers. |
| Indexed By | SCI ; SCIE |
| Language | 英语 |
| Funding Project | Science and Technology Commission of Shanghai Municipality[17YF1422200] ; Science and Technology Commission of Shanghai Municipality[17ZR1435400] |
| WOS Research Area | Immunology ; Research & Experimental Medicine |
| WOS Subject | Immunology ; Medicine, Research & Experimental |
| WOS ID | WOS:000424519300021 |
| Publisher | ROCKEFELLER UNIV PRESS |
| WOS Keyword | HIPPO SIGNALING PATHWAY ; ORGAN SIZE CONTROL ; INTERFERON REGULATORY FACTOR-3 ; MINOR APHTHOUS ULCERATION ; CELL CONTACT INHIBITION ; TUMOR-SUPPRESSOR ; INNATE IMMUNITY ; GROWTH-CONTROL ; INTESTINAL REGENERATION ; COLORECTAL-CANCER |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16272 |
| Collection | 生命科学与技术学院 生命科学与技术学院_特聘教授组_周兆才组 生命科学与技术学院_硕士生 |
| Corresponding Author | Jiao, Shi; Zhou, Zhaocai |
| Affiliation | 1.Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,Shanghai Inst B, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Fudan Univ, Dept Hematol, Zhongshan Hosp, Shanghai, Peoples R China 4.Fudan Univ, Inst Clin Sci, Zhongshan Hosp, Shanghai, Peoples R China |
| Corresponding Author Affilication | School of Life Science and Technology |
| Recommended Citation GB/T 7714 | Jiao, Shi,Guan, Jingmin,Chen, Min,et al. Targeting IRF3 as a YAP agonist therapy against gastric cancer[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2018,215(2):699-718. |
| APA | Jiao, Shi.,Guan, Jingmin.,Chen, Min.,Wang, Wenjia.,Li, Chuanchuan.,...&Zhou, Zhaocai.(2018).Targeting IRF3 as a YAP agonist therapy against gastric cancer.JOURNAL OF EXPERIMENTAL MEDICINE,215(2),699-718. |
| MLA | Jiao, Shi,et al."Targeting IRF3 as a YAP agonist therapy against gastric cancer".JOURNAL OF EXPERIMENTAL MEDICINE 215.2(2018):699-718. |
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