The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1
文献类型：期刊论文
| 作者 | Zhang, Boyi1,2; Chen, Fei1,2; Han, Liu1,2; Qian, Min1,2; Chin, Y. Eugene1,2; Sun, Yu1,2; Fu, Da3; Xu, Qixia4,5; Cong, Xianling6; Wu, Chunyan7 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2018 |
| 卷号 | 9期号:-页码:1723 |
| 关键词 | hepatocellular carcinoma (HCC) TGF-beta CXXC5 HDAC signaling regulation |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-018-04010-4 |
| 文献子类 | Article |
| 英文摘要 | The senescence-associated secretory phenotype (SASP) can be provoked by side effects of therapeutic agents, fueling advanced complications including cancer resistance. However, the intracellular signal network supporting initiation and development of the SASP driven by treatment-induced damage remains unclear. Here we report that the transcription factor Zscan4 is elevated for expression by an ATM-TRAF6-TAK1 axis during the acute DNA damage response and enables a long term SASP in human stromal cells. Further, TAK1 activates p38 and PI3K/Akt/mTOR to support the persistent SASP signaling. As TAK1 is implicated in dual feedforward mechanisms to orchestrate the SASP development, pharmacologically targeting TAK1 deprives cancer cells of resistance acquired from treatment-damaged stromal cells in vitro and substantially promotes tumour regression in vivo. Together, our study reveals a novel network that links functionally critical molecules associated with the SASP development in therapeutic settings, thus opening new avenues to improve clinical outcomes and advance precision medicine. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | INFLAMMATORY CYTOKINE SECRETION ; CANCER-THERAPY RESISTANCE ; EPITHELIAL-CELL LINE ; TUMOR MICROENVIRONMENT ; PARACRINE SENESCENCE ; DAMAGE ; NETWORK ; CHEMOSENSITIVITY ; TUMORIGENESIS ; CHEMOTHERAPY |
| 语种 | 英语 |
| WOS记录号 | WOS:000431113000011 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/733]  |
| 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.Shanghai Jiao Tong Univ, Univ Chinese Acad Sci, Sch Med, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China; 3.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Cent Lab Med Res, Shanghai 200072, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai 200031, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 6.Jilin Univ, China Japan Union Hosp, Tissue Bank, Changchun 130033, Jilin, Peoples R China; 7.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Pathol, Shanghai 200433, Peoples R China; 8.Ganzhou City Peoples Hosp, Jiangxi Prov Tumour Hosp, Dept Radiol, Nanchang 330029, Jiangxi, Peoples R China; 9.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Nucl Med, Shanghai 200072, Peoples R China; 10.Imperial Coll London, Dept Surg & Canc, London W12 0NN, England; |
| 推荐引用方式 GB/T 7714 | Zhang, Boyi,Chen, Fei,Han, Liu,et al. The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1[J]. NATURE COMMUNICATIONS,2018,9(-):1723. |
| APA | Zhang, Boyi.,Chen, Fei.,Han, Liu.,Qian, Min.,Chin, Y. Eugene.,...&,.(2018).The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1.NATURE COMMUNICATIONS,9(-),1723. |
| MLA | Zhang, Boyi,et al."The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1".NATURE COMMUNICATIONS 9.-(2018):1723. |
入库方式： OAI收割
来源：上海营养与健康研究所
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