XBP1 silencing decreases glioma cell viability and glycolysis possibly by inhibiting HK2 expression

Yaohua Liu; Xu Hou; Min Liu; Zhuowen Yang; Yunke Bi; Huichao Zou; Jianing Wu; Hui Che; Chenguang Li; Xiaoxiong Wang; Kaikai Wang; Chen Zhong; Jiakang Zhang; Tao Yu; Qilong Bian; Shuang Chai; Huailei Liu; Jing Ai; Shiguang Zhao

doi:10.1007/s11060-015-2003-y

XBP1 silencing decreases glioma cell viability and glycolysis possibly by inhibiting HK2 expression

J Neurooncol. 2016 Feb;126(3):455-62. doi: 10.1007/s11060-015-2003-y. Epub 2015 Dec 17.

Authors

Yaohua Liu¹, Xu Hou¹, Min Liu², Zhuowen Yang³, Yunke Bi¹, Huichao Zou⁴, Jianing Wu¹, Hui Che⁵, Chenguang Li¹, Xiaoxiong Wang¹, Kaikai Wang¹, Chen Zhong¹, Jiakang Zhang¹, Tao Yu¹, Qilong Bian¹, Shuang Chai¹, Huailei Liu¹, Jing Ai⁵, Shiguang Zhao⁶

Affiliations

¹ Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
² College of Basic Medicine, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
³ Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
⁴ Department of Pain Medicine, Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
⁵ Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
⁶ Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China. guangsz@hotmail.com.

PMID: 26680227
DOI: 10.1007/s11060-015-2003-y

Abstract

Glioma cells rely on glycolysis to obtain energy and sustain their survival under microenvironmental stress in vivo. The mechanisms of regulation of glycolysis in glioma cells are unclear. Signaling pathway mediated by the transcription factor X box-binding protein 1 (XBP1) is one of the most important pathways of unfolded protein response which is comprehensively activated in cancer cells upon the microenvironmental stress. Here we showed that XBP1 was significantly activated in glioma tissues in vivo. XBP1 silencing resulted in decreasing of glioma cell viability and ATP/lactate production under hypoxia, which is possibly mediated by inhibition of Hexokinase II (HK2)'s expression. More importantly, XBP1 silenced glioma cells showed the decrease of tumor formation capacity. Our results revealed that XBP1s activation was involved in glioma glycolysis regulation and might be a potential molecular target for glioma treatment.

Keywords: Cancer metabolism; Glioma; HK2; XBP1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Animals
Apoptosis*
Cell Proliferation
DNA-Binding Proteins / antagonists & inhibitors*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Female
Gene Silencing*
Glioma
Glycolysis*
Hexokinase / antagonists & inhibitors*
Hexokinase / genetics
Hexokinase / metabolism
Humans
Hypoxia / physiopathology
Lactic Acid / metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Oxygen Consumption
RNA, Small Interfering / genetics*
Rats, Wistar
Regulatory Factor X Transcription Factors
Signal Transduction
Transcription Factors / antagonists & inhibitors*
Transcription Factors / genetics
Transcription Factors / metabolism
Tumor Cells, Cultured
X-Box Binding Protein 1
Xenograft Model Antitumor Assays

Substances

DNA-Binding Proteins
RNA, Small Interfering
Regulatory Factor X Transcription Factors
Transcription Factors
X-Box Binding Protein 1
XBP1 protein, human
Xbp1 protein, mouse
Xbp1 protein, rat
Lactic Acid
Adenosine Triphosphate
Hexokinase