Metabolic rewiring in cancer cells overexpressing the glucocorticoid-induced leucine zipper protein (GILZ): Activation of mitochondrial oxidative phosphorylation and sensitization to oxidative cell death induced by mitochondrial targeted drugs

•GILZ promotes mitochondrial OXPHOS in cancer.•Metabolic reprograming induced by GILZ is associated with high proliferation rate.•Metabolic changes induced by GILZ sensitizes cancer cells to mitochondrial pro-oxidants. Cancer cell metabolism is largely controlled by oncogenic signals and nutrient av...

Full description

Saved in:
Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2017-04, Vol.85, p.166-174
Main Authors: André, Fanny, Trinh, Anne, Balayssac, Stéphane, Maboudou, Patrice, Dekiouk, Salim, Malet-Martino, Myriam, Quesnel, Bruno, Idziorek, Thierry, Kluza, Jérome, Marchetti, Philippe
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Cancer cell metabolism
Cell Death - drug effects
Cell Line, Tumor
Chemical Sciences
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Drug Delivery Systems
Flow Cytometry
Gene Expression - drug effects
Glucocorticoids
Glucocorticoids - pharmacology
Hydrazines - pharmacology
Metabolome - drug effects
Mice
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Oxidation-Reduction
Real-Time Polymerase Chain Reaction
ROS
Sulfides - pharmacology
Thiadiazoles - pharmacology
TSC-22
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•GILZ promotes mitochondrial OXPHOS in cancer.•Metabolic reprograming induced by GILZ is associated with high proliferation rate.•Metabolic changes induced by GILZ sensitizes cancer cells to mitochondrial pro-oxidants. Cancer cell metabolism is largely controlled by oncogenic signals and nutrient availability. Here, we highlighted that the glucocorticoid-induced leucine zipper (GILZ), an intracellular protein influencing many signaling pathways, reprograms cancer cell metabolism to promote proliferation. We provided evidence that GILZ overexpression induced a significant increase of mitochondrial oxidative phosphorylation as evidenced by the augmentation in basal respiration, ATP-linked respiration as well as respiratory capacity. Pharmacological inhibition of glucose, glutamine and fatty acid oxidation reduced the activation of GILZ-induced mitochondrial oxidative phosphorylation. At glycolysis level, GILZ-overexpressing cells enhanced the expression of glucose transporters in their plasmatic membrane and showed higher glycolytic reserve. 1H NMR metabolites quantification showed an up-regulation of amino acid biosynthesis. The GILZ-induced metabolic reprograming is present in various cancer cell lines regardless of their driver mutations status and is associated with higher proliferation rates persisting under metabolic stress conditions. Interestingly, high levels of OXPHOS made GILZ-overexpressing cells vulnerable to cell death induced by mitochondrial pro-oxidants. Altogether, these data indicate that GILZ reprograms cancer metabolism towards mitochondrial OXPHOS and sensitizes cancer cells to mitochondria-targeted drugs with pro-oxidant activities.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2017.02.011