AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness

doi:10.1016/j.devcel.2018.11.033

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 国家新药筛选中心

	AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness
	Wang, Xinbo 3,4,8; Jin, Jiali 3,8; Wan, Fangning 6,7; Zhao, Linlin 3,8; Chu, Hongshang 3; Chen, Cong 3; Liao, Guanghong 3; Liu, Jian 5; Yu, Yue 3; Teng, Hongqi 8
刊名	Developmental cell
	2018-12-21
ISSN号	1878-1551
DOI	10.1016/j.devcel.2018.11.033
文献子类	Article
英文摘要	NANOG is an essential transcriptional factor for the maintenance of embryonic stem cells (ESCs) and cancer stem cells (CSCs) in prostate cancer (PCa). However, the regulation mechanism of NANOG protein stability in cancer progression is still elusive. Here, we report that NANOG is degraded by SPOP, a frequently mutated tumor suppressor of PCa. Cancer-associated mutations of SPOP or the mutation of NANOG at S68Y abrogates the SPOP-mediated NANOG degradation, leading to elevated PCa cancer stemness and poor prognosis. In addition, SPOP-mediated NANOG degradation is controlled by the AMPK-BRAF signal axis through the phosphorylation of NANOG at Ser68, which blocked the interaction between SPOP and NANOG. Thus, our study provides a regulation mechanism of PCa stemness controlled by phosphorylation-mediated NANOG stability, which helps to identify novel drug targets and improve therapeutic strategy for PCa.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266351]
专题	国家新药筛选中心药物安全性评价中心
通讯作者	Ge, Xin; Ye, Dingwei; Wang, Ping
作者单位	1.Department of Clinical Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; 2.Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; 3.Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China; 4.Shanghai Putuo People's Hospital, School of Medicine, Tongji University, Shanghai 200060, China; 5.National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; 6.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 7.Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; 8.Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; 9.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
推荐引用方式 GB/T 7714	Wang, Xinbo,Jin, Jiali,Wan, Fangning,et al. AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness[J]. Developmental cell,2018.
APA	Wang, Xinbo.,Jin, Jiali.,Wan, Fangning.,Zhao, Linlin.,Chu, Hongshang.,...&Wang, Ping.(2018).AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness.Developmental cell.
MLA	Wang, Xinbo,et al."AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness".Developmental cell (2018).