HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity
文献类型：期刊论文
| 作者 | Wu, Shiying2,3; Zhang, Qian2,3; Zhang, Fei2,3; Meng, Fansen2,3,4,5; Liu, Shengduo2,3; Zhou, Ruyuan2,3; Wu, Qingzhe2,3; Li, Xinran2,3; Shen, Li2,3; Huang, Jun2,3 |
| 刊名 | NATURE CELL BIOLOGY
 |
| 出版日期 | 2019 |
| 卷号 | 21期号:8页码:1027-+ |
| ISSN号 | 1465-7392 |
| 关键词 | apoptosis autophagy cardiolipin mitophagy neuroprotection phospholipid |
| DOI | 10.1038/s41556-019-0352-z |
| 文献子类 | Article |
| 英文摘要 | Sensing cytosolic DNA through the cGAS-STING pathway constitutes a widespread innate immune mechanism to monitor cellular damage and microbial invasion. Evading this surveillance is crucial in tumorigenesis, but the process remains largely unexplored. Here, we show that the receptor tyrosine kinase HER2 (also known as ErbB-2 or Neu) potently inhibits cGAS-STING signalling and prevents cancer cells from producing cytokines, entering senescence and undergoing apoptosis. HER2, but not EGFR, associates strongly with STING and recruits AKT1 (also known as PKB) to directly phosphorylate TBK1, which prevents the TBK1-STING association and TBK1 K63-linked ubiquitination, thus attenuating STING signalling. Unexpectedly, we observed that DNA sensing robustly activates the HER2-AKT1 axis, resulting in negative feedback. Accordingly, genetic or pharmacological targeting of the HER2-AKT1 cascade augments damage-induced cellular senescence and apoptosis, and enhances STING-mediated antiviral and antitumour immunity. Thus, our findings reveal a critical function of the oncogenic pathway in innate immune regulation and unexpectedly connect HER2-AKT1 signalling to the surveillance of cellular damage and antitumour immunity. |
| 学科主题 | Cell Biology |
| WOS关键词 | GMP-AMP SYNTHASE ; INNATE IMMUNITY ; ACTIVATION ; CGAS ; TBK1 ; INFLAMMATION ; SENESCENCE ; RECEPTORS ; MECHANISM ; ADAPTER |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000478029000014 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1300]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Fujian Normal Univ, Coll Life Sci, Biomed Res Ctr South China, Key Lab Innate Immune Biol Fujian Prov, Fuzhou, Fujian, Peoples R China; 2.Zhejiang Univ, MOE Lab Biosyst Homeostasis & Protect, Life Sci Inst, Hangzhou, Zhejiang, Peoples R China; 3.Zhejiang Univ, Innovat Ctr Cell Signaling Network, Life Sci Inst, Hangzhou, Zhejiang, Peoples R China; 4.Zhejiang Univ, Dept Hepatobiliary & Pancreat Surg, Affiliated Hosp 1, Sch Med, Hangzhou, Zhejiang, Peoples R China; 5.Zhejiang Univ, Zhejiang Prov Key Lab Pancreat Dis, Affiliated Hosp 1, Sch Med, Hangzhou, Zhejiang, Peoples R China; 6.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China; 7.Zhengzhou Univ, Affiliated Hosp 1, Translat Med Ctr, Zhengzhou, Henan, Peoples R China; 8.Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA; 9.Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA; 10.Zhejiang Univ, Affiliated Hosp 2, Sch Med, Inst Translat Med,Eye Ctr, Hangzhou, Zhejiang, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Wu, Shiying,Zhang, Qian,Zhang, Fei,et al. HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity[J]. NATURE CELL BIOLOGY,2019,21(8):1027-+. |
| APA | Wu, Shiying.,Zhang, Qian.,Zhang, Fei.,Meng, Fansen.,Liu, Shengduo.,...&,.(2019).HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity.NATURE CELL BIOLOGY,21(8),1027-+. |
| MLA | Wu, Shiying,et al."HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity".NATURE CELL BIOLOGY 21.8(2019):1027-+. |
入库方式： OAI收割
来源：上海营养与健康研究所
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