Glutamine modulates expression and function of glucose 6-phosphate dehydrogenase via NRF2 in colon cancer cells

  • 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.
Author:Ibrahim H. Polat, Míriam Tarrado-Castellarnau, Adrian Benito, Claudia Hernandez-Carro, Josep Centelles, Silvia Marin, Marta CascanteORCiD
Parent Title (English):Antioxidants
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/08/25
Date of first Publication:2021/08/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/05/04
Tag:cancer cell metabolism; colon cancer; glucose-6-phosphate dehydrogenase; oxidative stress; pentose phosphate pathway
Issue:9, art. 1349
Page Number:16
First Page:1
Last Page:16
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).
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0