PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation

Handle URI:
http://hdl.handle.net/10754/346876
Title:
PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation
Authors:
Hou, Xu; Liu, Yaohua; Liu, Huailei; Chen, Xin; Liu, Min; Che, Hui; Guo, Fei; Wang, Chunlei; Zhang, Daming; Wu, Jianing; Chen, Xiaofeng; Shen, Chen; Li, Chenguang; Peng, Fei; Bi, Yunke; Yang, Zhuowen; Yang, Guang; Ai, Jing; Gao, Xin ( 0000-0002-7108-3574 ) ; Zhao, Shiguang
Abstract:
Glioma relies on glycolysis to obtain energy and sustain its survival under low glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis regulation are still unclear. Signaling mediated by Double-stranded RNA-activated protein kinase (PKR) - like ER kinase (PERK) is one of the important pathways of unfolded protein response (UPR) which is comprehensively activated in cancer cells upon the hypoxic and low glucose stress. Here we show that PERK is significantly activated in human glioma tissues. PERK silencing results in decreased glioma cell viability and ATP/lactate production upon low glucose stress, which is mediated by partially blocked AKT activation and subsequent inhibition of Hexokinase II (HK2)'s mitochondria translocation. More importantly, PERK silenced glioma cells show decreased tumor formation capacity. Our results reveal that PERK activation is involved in glioma glycolysis regulation and may be a potential molecular target for glioma treatment.
KAUST Department:
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation 2015, 5:9065 Scientific Reports
Publisher:
Nature Publishing Group
Journal:
Scientific Reports
Issue Date:
12-Mar-2015
DOI:
10.1038/srep09065
PubMed ID:
25761777
PubMed Central ID:
PMC4356960
Type:
Article
ISSN:
2045-2322
Additional Links:
http://www.nature.com/doifinder/10.1038/srep09065
Appears in Collections:
Articles; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorHou, Xuen
dc.contributor.authorLiu, Yaohuaen
dc.contributor.authorLiu, Huaileien
dc.contributor.authorChen, Xinen
dc.contributor.authorLiu, Minen
dc.contributor.authorChe, Huien
dc.contributor.authorGuo, Feien
dc.contributor.authorWang, Chunleien
dc.contributor.authorZhang, Damingen
dc.contributor.authorWu, Jianingen
dc.contributor.authorChen, Xiaofengen
dc.contributor.authorShen, Chenen
dc.contributor.authorLi, Chenguangen
dc.contributor.authorPeng, Feien
dc.contributor.authorBi, Yunkeen
dc.contributor.authorYang, Zhuowenen
dc.contributor.authorYang, Guangen
dc.contributor.authorAi, Jingen
dc.contributor.authorGao, Xinen
dc.contributor.authorZhao, Shiguangen
dc.date.accessioned2015-03-19T07:37:51Zen
dc.date.available2015-03-19T07:37:51Zen
dc.date.issued2015-03-12en
dc.identifier.citationPERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation 2015, 5:9065 Scientific Reportsen
dc.identifier.issn2045-2322en
dc.identifier.pmid25761777en
dc.identifier.doi10.1038/srep09065en
dc.identifier.urihttp://hdl.handle.net/10754/346876en
dc.description.abstractGlioma relies on glycolysis to obtain energy and sustain its survival under low glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis regulation are still unclear. Signaling mediated by Double-stranded RNA-activated protein kinase (PKR) - like ER kinase (PERK) is one of the important pathways of unfolded protein response (UPR) which is comprehensively activated in cancer cells upon the hypoxic and low glucose stress. Here we show that PERK is significantly activated in human glioma tissues. PERK silencing results in decreased glioma cell viability and ATP/lactate production upon low glucose stress, which is mediated by partially blocked AKT activation and subsequent inhibition of Hexokinase II (HK2)'s mitochondria translocation. More importantly, PERK silenced glioma cells show decreased tumor formation capacity. Our results reveal that PERK activation is involved in glioma glycolysis regulation and may be a potential molecular target for glioma treatment.en
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://www.nature.com/doifinder/10.1038/srep09065en
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.titlePERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocationen
dc.typeArticleen
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalScientific Reportsen
dc.identifier.pmcidPMC4356960en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of Chinaen
dc.contributor.institutionCollege of Basic Medicine, Beijing University of Chinese Medicine, Beijing, People's Republic of Chinaen
dc.contributor.institutionDepartment of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of Chinaen
dc.contributor.institutionDepartment of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of Chinaen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorGao, Xinen

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