Knockdown of the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Sensitizes Glioma Cells to Hypoxia, Irradiation and Temozolomide

被引：19
|
作者：
Maurer, Gabriele D. [1 ,2 ,3 ,4 ]
Heller, Sonja [1 ,2 ,3 ,4 ]
Wanka, Christina [1 ,2 ,3 ,4 ]
Rieger, Johannes [1 ,2 ,3 ,4 ,5 ]
Steinbach, Joachim P. [1 ,2 ,3 ,4 ]
机构：
[1] Goethe Univ, Univ Hosp Frankfurt, Dr Senckenberg Inst Neurooncol, D-60590 Frankfurt, Germany
[2] Goethe Univ, Univ Hosp Frankfurt, Univ Canc Ctr UCT, D-60590 Frankfurt, Germany
[3] German Canc Res Ctr DKFZ Heidelberg, D-60590 Frankfurt, Germany
[4] German Canc Consortium DKTK, Partner Site Frankfurt Mainz, D-60590 Frankfurt, Germany
[5] Eberhard Karls Univ Tubingen, Univ Hosp Tuebingen, Hertie Inst Clin Brain Res, Interdisciplinary Div Neurooncol, D-72076 Tubingen, Germany
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 05期
关键词：
TP53-induced glycolysis and apoptosis regulator; glioma; hypoxia; irradiation; temozolomide; reactive oxygen species; hypoxia-inducible factor; TUMOR-SUPPRESSOR; P53; GLIOBLASTOMA; RADIOSENSITIZATION; MICROENVIRONMENT; IDENTIFICATION; PROGRESSION; PROGNOSIS; PROTECTS; HIF-1;
D O I：
10.3390/ijms20051061
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to decrease glycolysis, to activate the pentose phosphate pathway, and to provide protection against oxidative damage. Hypoxic regions are considered characteristic of glioblastoma and linked with resistance to current treatment strategies. Here, we established that LNT-229 glioma cell lines stably expressed shRNA constructs targeting TIGAR, and exposed them to hypoxia, irradiation and temozolomide. The disruption of TIGAR enhanced levels of reactive oxygen species and cell death under hypoxic conditions, as well as the effectiveness of irradiation and temozolomide. In addition, TIGAR was upregulated by HIF-1. As a component of a complex network, TIGAR contributes to the metabolic adjustments that arise from either spontaneous or therapy-induced changes in tumor microenvironment.
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页数：14
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