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

Xu Hou, Yaohua Liu, Huailei Liu, Xin Chen, Min Liu, Hui Che, Fei Guo, Chunlei Wang, Daming Zhang, Jianing Wu, Xiaofeng Chen, Chen Shen, Chenguang Li, Fei Peng, Yunke Bi, Zhuowen Yang, Guang Yang, Jing Ai, Xin Gao, SHIGUANG ZHAO

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.
Original languageEnglish (US)
JournalScientific Reports
Volume5
Issue number1
DOIs
StatePublished - Mar 12 2015

Fingerprint

Dive into the research topics of 'PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation'. Together they form a unique fingerprint.

Cite this