TY - JOUR A1 - Maurer, Gabriele D. A1 - Heller, Sonja A1 - Wanka, Christina A1 - Rieger, Johannes A1 - Steinbach, Joachim Peter T1 - Knockdown of the TP53-induced glycolysis and apoptosis regulator (TIGAR) sensitizes glioma cells to hypoxia, irradiation and temozolomide T2 - International journal of molecular sciences N2 - 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. KW - TP53-induced glycolysis and apoptosis regulator KW - glioma KW - hypoxia KW - irradiation KW - temozolomide KW - reactive oxygen species KW - hypoxia-inducible factor Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48475 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-484757 SN - 1422-0067 SN - 1661-6596 N1 - 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). VL - 20 IS - 5, Art. 1061 SP - 1 EP - 14 PB - Molecular Diversity Preservation International CY - Basel ER -