Targeting IRF3 as a YAP agonist therapy against gastric cancer | |
Jiao, Shi1; Guan, Jingmin1; Chen, Min1; Wang, Wenjia1; Li, Chuanchuan1; Zhou, Zhaocai1,2; Wang, Yugong2; Cheng, Yunfeng3,4 | |
刊名 | JOURNAL OF EXPERIMENTAL MEDICINE |
2018 | |
卷号 | 215期号:2页码:699-718 |
关键词 | 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 |
ISSN号 | 0022-1007 |
DOI | 10.1084/jem.20171116 |
文献子类 | Article |
英文摘要 | 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. |
电子版国际标准刊号 | 1540-9538 |
WOS研究方向 | Immunology ; Medicine, Research & Experimental |
语种 | 英语 |
WOS记录号 | WOS:000424519300021 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3487] |
专题 | 生化所2018年发文 上海生化细胞研究所_上海生科院生化细胞研究所 |
通讯作者 | Jiao, Shi; Zhou, Zhaocai |
作者单位 | 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 |
推荐引用方式 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.,...&Cheng, Yunfeng.(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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