The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1

doi:10.1038/s41467-019-10074-7

GSTDTAP > 资源环境科学

DOI	10.1038/s41467-019-10074-7
	The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1
	Zhang, Boyi 1,2; Fu, Da 3; Xu, Qixia 4,5; Cong, Xianling 6; Wu, Chunyan 7; Zhong, Xiaoming 8; Ma, Yushui 9; Lv, Zhongwei 9; Chen, Fei 1,2; Han, Liu 1,2; Qian, Min 1,2; Chin, Y. Eugene 1,2; Lam, Eric W. -F.10; Chiao, Paul 11; Sun, Yu 1,2,12,13
	2019-05-01
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2018
卷号	9
文章类型	Article
语种	英语
国家	Peoples R China; England; USA
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.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000431113000011
WOS关键词	INFLAMMATORY CYTOKINE SECRETION ; CANCER-THERAPY RESISTANCE ; EPITHELIAL-CELL LINE ; TUMOR MICROENVIRONMENT ; PARACRINE SENESCENCE ; DAMAGE ; NETWORK ; CHEMOSENSITIVITY ; TUMORIGENESIS ; CHEMOTHERAPY
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/204349
专题	资源环境科学
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China; 2.Shanghai Jiao Tong Univ, Univ Chinese Acad Sci, Sch Med, 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; 11.Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA; 12.Univ Washington, Dept Med, Seattle, WA 98195 USA; 13.Univ Washington, VAPSHCS, Seattle, WA 98195 USA
推荐引用方式 GB/T 7714	Zhang, Boyi,Fu, Da,Xu, Qixia,et al. The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1[J]. NATURE COMMUNICATIONS,2019,9.
APA	Zhang, Boyi.,Fu, Da.,Xu, Qixia.,Cong, Xianling.,Wu, Chunyan.,...&Sun, Yu.(2019).The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1.NATURE COMMUNICATIONS,9.
MLA	Zhang, Boyi,et al."The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1".NATURE COMMUNICATIONS 9(2019).