Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

Contat, Caroline; Ancey, Pierre-Benoit; Zangger, Nadine; Sabatino, Silvia; Pascual, Justine; Escrig, Stéphane; Jensen, Louise; Goepfert, Christine; Lanz, Bernard; Lepore, Mario; Gruetter, Rolf; Rossier, Anouk; Berezowska, Sabina; Neppl, Christina; Zlobec, Inti; Clerc-Rosset, Stéphanie; Knott, Graham William; Rathmell, Jeffrey C; Abel, E Dale; Meibom, Anders; ... (2020). Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth. eLife, 9 eLife Sciences Publications 10.7554/eLife.53618

[img]
Preview
Text
elife-53618-v1.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology

UniBE Contributor:

Göpfert, Christine and Zlobec, Inti

Subjects:

600 Technology > 630 Agriculture

ISSN:

2050-084X

Publisher:

eLife Sciences Publications

Language:

English

Submitter:

Inti Zlobec

Date Deposited:

11 Mar 2021 12:20

Last Modified:

11 Mar 2021 12:25

Publisher DOI:

10.7554/eLife.53618

PubMed ID:

32571479

Uncontrolled Keywords:

NanoSIMS cancer biology genetically engineered mouse model of cancer glucose transporters human lamellar bodies lung adenocarcinoma mouse

BORIS DOI:

10.48350/150077

URI:

https://boris.unibe.ch/id/eprint/150077

Actions (login required)

Edit item Edit item
Provide Feedback