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Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

by Marin, Silvia , Polat, Ibrahim H. , Hernandez-Carro, Claudia , Benito, Adrian , Cascante, Marta , Tarrado-Castellarnau, Míriam , Centelles, Josep

in Amino acids / Antibiotics / Apoptosis / Biosynthesis / Breast cancer / cancer cell metabolism / catabolism / Cell cycle / cell cycle checkpoints / Cell growth / Cell proliferation / Colon cancer / Colorectal cancer / colorectal neoplasms / Dehydrogenases / Enzymes / Gene expression / Glucose / glucose 6-phosphate / Glucose metabolism / glucose-6-phosphate dehydrogenase / Glucosephosphate dehydrogenase / Glutamine / Metabolism / NADP-glucose-6-phosphate dehydrogenase / neoplasm cells / Nucleotides / oxidative stress / pentose phosphate cycle / Pentose phosphate pathway / phenotype / Phenotypes / Ribose / Tumors

2021

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Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

by Marin, Silvia , Polat, Ibrahim H. , Hernandez-Carro, Claudia , Benito, Adrian , Cascante, Marta , Tarrado-Castellarnau, Míriam , Centelles, Josep

2021

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Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

by Marin, Silvia , Polat, Ibrahim H. , Hernandez-Carro, Claudia , Benito, Adrian , Cascante, Marta , Tarrado-Castellarnau, Míriam , Centelles, Josep

2021

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Journal Article

Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

Marin, Silvia,

Polat, Ibrahim H.,

Hernandez-Carro, Claudia,

Benito, Adrian,

Cascante, Marta,

Tarrado-Castellarnau, Míriam,

Centelles, Josep

2021

Overview

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.

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Publisher

MDPI AG,MDPI

Subject

/ cancer cell metabolism

/ catabolism