Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition
文献类型：期刊论文
| 作者 | Wang, Weixuan1; Hu, Yadong1,2; Yang, Changmei1; Zhu, Songbiao1; Wang, Xiaofei1; Zhang, Zhenyu3; Deng, Haiteng1 |
| 刊名 | MOLECULAR & CELLULAR PROTEOMICS
 |
| 出版日期 | 2018-10-01 |
| 卷号 | 17期号:10页码:2005-2017 |
| ISSN号 | 1535-9476 |
| DOI | 10.1074/mcp.RA118.000882 |
| 产权排序 | 2 |
| 文献子类 | Article |
| 英文摘要 | Nicotinamide adenine dinucleotide (NAD) plays an essential role in all aspects of human life. NAD levels decrease as humans age, and supplementation with NAD precursors plays a protective role against aging and associated disease. Less is known about the effects of decreased NAD on cellular processes, which is the basis for understanding the relationship between cellular NAD levels and aging-associated disease. In the present study, cellular NAD levels were decreased by overexpression of CD38, a NAD hydrolase, or by treating cells with FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). Quantitative proteomics revealed that declining NAD levels downregulated proteins associated with primary metabolism and suppressed cell growth in culture and nude mice. Decreased glutathione synthesis caused a 4-fold increase in cellular reactive oxygen species levels, and more importantly upregulated proteins related to movement and adhesion. In turn, this significantly changed cell morphology and caused cells to undergo epithelial to mesenchymal transition (EMT). Secretomic analysis also showed that decreased NAD triggered interleukin-6 and transforming growth factor beta (TGF) secretion, which activated integrin--catenin, TGF-MAPK, and inflammation signaling pathways to sustain the signaling required for EMT. We further revealed that decreased NAD inactivated sirtuin 1, resulting in increased signal transducer and activator of transcription 3 (STAT3) acetylation and phosphorylation, and STAT3 activation. Repletion of nicotinamide or nicotinic acid inactivated STAT3 and reversed EMT, as did STAT3 inhibition. Taken together, these results indicate that decreased NAD activates multiple signaling pathways to promote EMT and suggests that age-dependent decreases in NAD may contribute to tumor progression. Consequently, repletion of NAD precursors has potential benefits for inhibiting cancer progression. |
| 学科主题 | Chemistry ; Analysis |
| URL标识 | 查看原文 |
| WOS关键词 | DIET-INDUCED OBESITY ; NICOTINAMIDE MONONUCLEOTIDE ; SERINE PHOSPHORYLATION ; MAXIMAL ACTIVATION ; CELLULAR NAD ; STEM-CELLS ; MITOCHONDRIAL ; CD38 ; METABOLISM ; MECHANISM |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| WOS记录号 | WOS:000445997400010 |
| 源URL | [http://210.75.237.14/handle/351003/30142]  |
| 专题 | 环境治理与食品安全领域_农业生物技术研究 |
| 作者单位 | 1.Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China; 2.Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Sichuan, Peoples R China; 3.Capital Med Univ, Beijing Chaoyang Hosp, Beijing 100043, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Weixuan,Hu, Yadong,Yang, Changmei,et al. Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition[J]. MOLECULAR & CELLULAR PROTEOMICS,2018,17(10):2005-2017. |
| APA | Wang, Weixuan.,Hu, Yadong.,Yang, Changmei.,Zhu, Songbiao.,Wang, Xiaofei.,...&Deng, Haiteng.(2018).Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition.MOLECULAR & CELLULAR PROTEOMICS,17(10),2005-2017. |
| MLA | Wang, Weixuan,et al."Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition".MOLECULAR & CELLULAR PROTEOMICS 17.10(2018):2005-2017. |
入库方式： OAI收割
来源：成都生物研究所
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