TY  - JOUR
A1  - Polat, Ibrahim H.
A1  - Tarrado-Castellarnau, Míriam
A1  - Benito, Adrian
A1  - Hernandez-Carro, Claudia
A1  - Centelles, Josep
A1  - Marin, Silvia
A1  - Cascante, Marta
T1  - Glutamine modulates expression and function of glucose 6-phosphate dehydrogenase via NRF2 in colon cancer cells
T2  - Antioxidants
N2  - Nucleotide pools need to be constantly replenished in cancer cells to support cell proliferation. The synthesis of nucleotides requires glutamine and 5-phosphoribosyl-1-pyrophosphate produced from ribose-5-phosphate via the oxidative branch of the pentose phosphate pathway (ox-PPP). Both PPP and glutamine also play a key role in maintaining the redox status of cancer cells. Enhanced glutamine metabolism and increased glucose 6-phosphate dehydrogenase (G6PD) expression have been related to a malignant phenotype in tumors. However, the association between G6PD overexpression and glutamine consumption in cancer cell proliferation is still incompletely understood. In this study, we demonstrated that both inhibition of G6PD and glutamine deprivation decrease the proliferation of colon cancer cells and induce cell cycle arrest and apoptosis. Moreover, we unveiled that glutamine deprivation induce an increase of G6PD expression that is mediated through the activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2). This crosstalk between G6PD and glutamine points out the potential of combined therapies targeting oxidative PPP enzymes and glutamine catabolism to combat colon cancer.
KW  - cancer cell metabolism
KW  - glucose-6-phosphate dehydrogenase
KW  - pentose phosphate pathway
KW  - colon cancer
KW  - oxidative stress
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62182
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621821
SN  - 2076-3921
N1  - This work was supported by MCIU/AEI/FEDER, UE (SAF2017-89673-R) and by MICINN/AEI/-European Commission FEDER funds—“Una manera de hacer Europa” (PID2020- 115051RB-I00), by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR)—Generalitat de Catalunya (2017SGR1033), and by Instituto de Salud Carlos III (CIBEREHD, CB17/04/00023). M.C. also received support through the prize “ICREA Academia” for excellence in research, funded by ICREA foundation–Generalitat de Catalunya. I.H.P. was supported by the EU grant Metaflux FP7-PTIN-GA-2010-264780. A.B. was supported by a Grant from CSIC (Programa JAE Predoc).
VL  - 10
IS  - 9, art. 1349
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel
ER  -