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Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth

Authors :
Caroline Contat
Pierre-Benoit Ancey
Nadine Zangger
Silvia Sabatino
Justine Pascual
Stéphane Escrig
Louise Jensen
Christine Goepfert
Bernard Lanz
Mario Lepore
Rolf Gruetter
Anouk Rossier
Sabina Berezowska
Christina Neppl
Inti Zlobec
Stéphanie Clerc-Rosset
Graham William Knott
Jeffrey C Rathmell
E Dale Abel
Anders Meibom
Etienne Meylan
Source :
eLife, Vol 9 (2020)
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

Glucose utilization increases in tumors, a metabolic process that is observed clinically by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development. 18F-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which is mainly dependent on Glut1. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we also report the presence of lamellar body-like organelles in tumor cells accumulating glucose-derived biomass, depending partially on Glut1. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma, the dual blockade of which could reach therapeutic responses not achieved by individual targeting.

Details

Language :
English
ISSN :
2050084X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.3aba89d5d7741e7b31b5d7c0de19941
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.53618