TY  - JOUR
A1  - Heller, Sonja
A1  - Maurer, Gabriele D.
A1  - Wanka, Christina
A1  - Hofmann, Ute
A1  - Luger, Anna-Luisa
A1  - Bruns, Ines
A1  - Steinbach, Joachim Peter
A1  - Rieger, Johannes
T1  - Gene suppression of transketolase-like protein 1 (TKTL1) sensitizes glioma cells to hypoxia and ionizing radiation
T2  - International journal of molecular sciences
N2  - In several tumor entities, transketolase-like protein 1 (TKTL1) has been suggested to promote the nonoxidative part of the pentose phosphate pathway (PPP) and thereby to contribute to a malignant phenotype. However, its role in glioma biology has only been sparsely documented. In the present in vitro study using LNT-229 glioma cells, we analyzed the impact of TKTL1 gene suppression on basic metabolic parameters and on survival following oxygen restriction and ionizing radiation. TKTL1 was induced by hypoxia and by hypoxia-inducible factor-1α (HIF-1α). Knockdown of TKTL1 via shRNA increased the cells’ demand for glucose, decreased flux through the PPP and promoted cell death under hypoxic conditions. Following irradiation, suppression of TKTL1 expression resulted in elevated levels of reactive oxygen species (ROS) and reduced clonogenic survival. In summary, our results indicate a role of TKTL1 in the adaptation of tumor cells to oxygen deprivation and in the acquisition of radioresistance. Further studies are necessary to examine whether strategies that antagonize TKTL1 function will be able to restore the sensitivity of glioma cells towards irradiation and antiangiogenic therapies in the more complex in vivo environment.
KW  - transketolase-like protein 1
KW  - pentose phosphate pathway
KW  - glioma
KW  - hypoxia
KW  - radiation
KW  - metabolism
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46894
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-468947
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  - 19
IS  - 8, Art. 2168
SP  - 1
EP  - 13
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -