title: PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation.
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.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Huailei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Basic Medicine, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Che
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Daming
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Yunke
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Zhuowen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.affiliation: Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D005947:Glucose / Q000378:metabolism*; D064593:Heterografts; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D013312:Stress, Physiological; D019892:eIF-2 Kinase / Q000235:genetics*
chemical_list: D005947:Glucose; D006593:Hexokinase; D051057:Proto-Oncogene Proteins c-akt; D019892:eIF-2 Kinase