Pemetrexed Hinders Translation Inhibition upon Low Glucose in Non-Small Cell Lung Cancer Cells - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue Metabolites Année : 2021

Pemetrexed Hinders Translation Inhibition upon Low Glucose in Non-Small Cell Lung Cancer Cells

Résumé

Genetic alterations in non-small cell lung cancers (NSCLC) stimulate the generation of energy and biomass to promote tumor development. However, the efficacy of the translation process is finely regulated by stress sensors, themselves often controlled by nutrient availability and chemotoxic agents. Yet, the crosstalk between therapeutic treatment and glucose availability on cell mass generation remains understudied. Herein, we investigated the impact of pemetrexed (PEM) treatment, a first-line agent for NSCLC, on protein synthesis, depending on high or low glucose availability. PEM treatment drastically repressed cell mass and translation when glucose was abundant. Surprisingly, inhibition of protein synthesis caused by low glucose levels was partially dampened upon co-treatment with PEM. Moreover, PEM counteracted the elevation of the endoplasmic reticulum stress (ERS) signal produced upon low glucose availability, providing a molecular explanation for the differential impact of the drug on translation according to glucose levels. Collectively, these data indicate that the ERS constitutes a molecular crosstalk between microenvironmental stressors, contributing to translation reprogramming and proteostasis plasticity.

Domaines

Cancer
Fichier principal
Vignette du fichier
metabolites-11-00198-v2.pdf (1.38 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03194581 , version 1 (09-04-2021)

Licence

Paternité

Identifiants

Citer

Marie Piecyk, Mouna Triki, Pierre-Alexandre Laval, Helena Dragic, Laura Cussonneau, et al.. Pemetrexed Hinders Translation Inhibition upon Low Glucose in Non-Small Cell Lung Cancer Cells. Metabolites, 2021, 11 (4), ⟨10.3390/metabo11040198⟩. ⟨hal-03194581⟩
132 Consultations
78 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More