1. Pemetrexed Hinders Translation Inhibition upon Low Glucose in Non-Small Cell Lung Cancer Cells
- Author
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Laura Cussonneau, Toufic Renno, Nicolas Aznar, Marie Piecyk, Helena Dragic, Cédric Chaveroux, Cédric Duret, Serge N. Manie, Pierre-Alexandre Laval, Carole Ferraro-Peyret, Joelle Fauvre, Mouna Triki, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), This work was supported by the Cancéropôle Lyon Auvergne Rhône-Alpes (R19152CC, R19075CC), Region Auvergne Rhone-Alpes (19 010898 01—41024), Fondation ARC pour Recherche sur le Cancer (R16173CC), Ligue Nationale contre le Cancer (R17167CC, R19007CC), PLASCAN (BioMHet, MiStiM’Plast, 17IA66 ANR-PLASCAN-MEHLEN), CNRS Prematuration program (NA-7-07-20) and Marie Sklodowska-Curie fellowship (grant agreement n°839398), ANR-17-CONV-0002,PLASCAN,Institut François Rabelais pour la recherche multidisciplinaire sur le cancer(2017), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Jonchère, Laurent, and Institut François Rabelais pour la recherche multidisciplinaire sur le cancer - - PLASCAN2017 - ANR-17-CONV-0002 - CONV - VALID
- Subjects
0301 basic medicine ,protein synthesis ,Endocrinology, Diabetes and Metabolism ,Cell ,lcsh:QR1-502 ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,NSCLC ,Biochemistry ,lcsh:Microbiology ,Article ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,medicine ,Protein biosynthesis ,pemetrexed ,Molecular Biology ,Chemistry ,ER stress signaling ,Endoplasmic reticulum ,Translation (biology) ,Cell biology ,glucose availability ,Crosstalk (biology) ,030104 developmental biology ,medicine.anatomical_structure ,Pemetrexed ,Proteostasis ,030220 oncology & carcinogenesis ,Reprogramming ,medicine.drug - Abstract
International audience; 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.
- Published
- 2021
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