Targeting beta 2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2+

	Targeting beta 2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2+
	Li, Shirong 1,2; Dai, Zhi 1; Yang, Dong 1; Li, Wenxuan 3; Dai, Hongjuan 1; Sun, Bin 1; Liu, Xiuyun 1,2; Xie, Xin 4; Xu, Rong 5; Zhao, Xudong 1,6,7
刊名	AMERICAN JOURNAL OF CANCER RESEARCH
	2019
卷号	9 期号:6 页码:1293-+
关键词	ATP1B2 Na+/K+-ATPase glioblastoma digoxin
ISSN号	2156-6976
通讯作者	Zhao, Xudong(ZHaoxudong@mail.kiz.ac.cn)
英文摘要	Glioblastoma (GBM) is the most frequent brain cancer with poor prognosis and few therapies and urgently requires effective treatments. Na+/K+-ATPase is considered as a target for GBM therapy and development of anticancer drugs. Cardiac glycosides bind the Na+/K+-ATPase a subunit to inhibit enzymatic activity and are promising candidates for anticancer drug development including GBM. However, the comparatively higher doses required for effective anticancer actions cause severe cardiotoxicity. Selectively targeting the ATPase Na+/K+ transporting subunit beta 2 (ATP1B2) that is not expressed in the heart might avoid the cardiotoxicity. However, the effect of targeting ATP1B2 in GBM remains unknown. In this study, we found that high ATP1B2 expression is significantly associated with poor prognosis of patients with GBM. ATP1B2 silencing in GBM cells resulted in remarkably cell cycle arrest at the G2/M phase and apoptosis with concomitant increase in intracellular Ca2+ and activation of p38 kinase, similar to Na+/K+-ATPase inhibition by the classic cardiac glycoside digoxin. ATP1B2 is expressed higher in glioblastoma stem-like cells (GSCs) than in GBM cells and its downregulation induces apoptosis of GSCs. Furthermore, inducible ATP1B2 knockdown significantly inhibit tumor growth in vivo. Our data suggest ATP1B2 has potential as a therapeutic target for GBM.
资助项目	Application of basic research project in Yunnan province[2016FB147] ; National Natural Science Foundation of China[81472862] ; National Natural Science Foundation of China[81802976]
WOS关键词	SODIUM-PUMP ; ADHESION MOLECULE ; K+-ATPASE ; P38 MAPK ; NA,K-ATPASE ; CALCIUM ; CANCER ; EXPRESSION ; HETEROGENEITY ; DIVERSITY
WOS研究方向	Oncology
语种	英语
出版者	E-CENTURY PUBLISHING CORP
WOS记录号	WOS:000473286300017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289287]
专题	中国科学院上海药物研究所
通讯作者	Zhao, Xudong
作者单位	1.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Chinese Acad Sci & Yunnan Prov, Key Lab Bioact Peptides Yunnan Prov,Kunming Inst, 32 East Jiaochang Rd, Kunming 650223, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650204, Yunnan, Peoples R China 3.Sichuan Univ, Coll Life Sci, Chengdu 610064, Sichuan, Peoples R China 4.Chinese Acad Sci, Stake Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200040, Peoples R China 6.Chinese Acad Sci, CAS Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China 7.Kunming Key Lab Hlth Aging Mol Mech Study, Kunming 650223, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Li, Shirong,Dai, Zhi,Yang, Dong,et al. Targeting beta 2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2+[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2019,9(6):1293-+.
APA	Li, Shirong.,Dai, Zhi.,Yang, Dong.,Li, Wenxuan.,Dai, Hongjuan.,...&Zhao, Xudong.(2019).Targeting beta 2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2+.AMERICAN JOURNAL OF CANCER RESEARCH,9(6),1293-+.
MLA	Li, Shirong,et al."Targeting beta 2 subunit of Na+/K+-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca2+".AMERICAN JOURNAL OF CANCER RESEARCH 9.6(2019):1293-+.