Targeting IRF3 as a YAP agonist therapy against gastric cancer

doi:10.1084/jem.20171116

	Targeting IRF3 as a YAP agonist therapy against gastric cancer
	Jiao, Shi 1; Guan, Jingmin 1; Chen, Min 1; Wang, Wenjia 1; Li, Chuanchuan 1; Wang, Yugong2 ; Cheng, Yunfeng 3,4; Zhou, Zhaocai1,2
	2018-02
发表期刊	JOURNAL OF EXPERIMENTAL MEDICINE
ISSN	0022-1007
卷号	215 期号:2 页码:699-718
发表状态	已发表
DOI	10.1084/jem.20171116
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.
收录类别	SCI ; SCIE
语种	英语
资助项目	Science and Technology Commission of Shanghai Municipality[17YF1422200] ; Science and Technology Commission of Shanghai Municipality[17ZR1435400]
WOS研究方向	Immunology ; Research & Experimental Medicine
WOS类目	Immunology ; Medicine, Research & Experimental
WOS记录号	WOS:000424519300021
出版者	ROCKEFELLER UNIV PRESS
WOS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
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16272
专题	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
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
通讯作者单位	生命科学与技术学院
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.,...&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.