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

被引：0
作者：
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
机构：
[1] First Affiliated Hospital of Harbin Medical University,Department of Neurosurgery
[2] Beijing University of Chinese Medicine,College of Basic Medicine
[3] First Affiliated Hospital of Harbin Medical University,Department of Endocrinology
[4] Cancer Hospital of Harbin Medical University,Department of Pain Medicine
[5] Harbin Medical University,Department of Pharmacology (State
来源：
Journal of Neuro-Oncology | 2016年 / 126卷
关键词：
XBP1; Glioma; Cancer metabolism; HK2;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
引用
收藏
页码：455 / 462
页数：7
相关论文
共 223 条
  • [1] Kathagen A(2013)Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells Acta Neuropathol 126 763-780
  • [2] Schulte A(2011)Hallmarks of cancer: the next generation Cell 144 646-674
  • [3] Balcke G(2013)Nodal regulates energy metabolism in glioma cells by inducing expression of hypoxia-inducible factor 1alpha Neuro-oncology 15 1330-1341
  • [4] Phillips HS(2011)Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme J Exp Med 208 313-326
  • [5] Martens T(2014)The impact of the endoplasmic reticulum protein-folding environment on cancer development Nat Rev Cancer 14 581-597
  • [6] Matschke J(2002)IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA Nature 415 92-96
  • [7] Günther HS(2002)IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response Genes Dev 16 452-466
  • [8] Soriano R(2001)XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor Cell 107 881-891
  • [9] Modrusan Z(2012)The unfolded protein response: controlling cell fate decisions under ER stress and beyond Nat Rev Mol Cell Biol 13 89-102
  • [10] Sandmann T(2003)XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response Mol Cell Biol 23 7448-7459
12345678910