Knockdown of the TP53-induced glycolysis and apoptosis regulator (TIGAR) sensitizes glioma cells to hypoxia, irradiation and temozolomide

  • 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-1α. 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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Author:Gabriele D. MaurerORCiDGND, Sonja HellerORCiD, Christina Wanka, Johannes Rieger, Joachim Peter SteinbachORCiDGND
Pubmed Id:
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/03/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/03/12
Tag:TP53-induced glycolysis and apoptosis regulator; glioma; hypoxia; hypoxia-inducible factor; irradiation; reactive oxygen species; temozolomide
Issue:5, Art. 1061
Page Number:14
First Page:1
Last Page:14
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0