GLUT3 is induced during epithelial-mesenchymal transition and promotes tumor cell proliferation in non-small cell lung cancer
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2049-3002-2-11.pdf
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Author(s)
Masin, Mark
Vazquez, Jessica
Rossi, Simona
Groeneveld, Svenja
Samson, Natasha
Schwalie, Petra C
Deplancke, Bart
Moradpour, Darius
Oliver, Trudy
Meylan, Etienne
Date Issued
July 2014
Journal
Cancer & Metabolism
Publisher
BioMed Central Ltd
Citation
Masin, Mark, Jessica Vazquez, Simona Rossi, Svenja Groeneveld, Natasha Samson, Petra C Schwalie, Bart Deplancke, et al. “GLUT3 is induced during epithelial-mesenchymal transition and promotes tumor cell proliferation in non-small cell lung cancer.” Cancer & Metabolism 2, no. 1 (2014): 11.
Version
Final published version
Abstract
Background:
Alterations in glucose metabolism and epithelial-mesenchymal transition (EMT) constitute two important characteristics of carcinoma progression toward invasive cancer. Despite an extensive characterization of each of them separately, the links between EMT and glucose metabolism of tumor cells remain elusive. Here we show that the neuronal glucose transporter GLUT3 contributes to glucose uptake and proliferation of lung tumor cells that have undergone an EMT.
Results:
Using a panel of human non-small cell lung cancer (NSCLC) cell lines, we demonstrate that GLUT3 is strongly expressed in mesenchymal, but not epithelial cells, a finding corroborated in hepatoma cells. Furthermore, we identify that ZEB1 binds to the GLUT3 gene to activate transcription. Importantly, inhibiting GLUT3 expression reduces glucose import and the proliferation of mesenchymal lung tumor cells, whereas ectopic expression in epithelial cells sustains proliferation in low glucose. Using a large microarray data collection of human NSCLCs, we determine that GLUT3 expression correlates with EMT markers and is prognostic of poor overall survival.
Conclusions:
Altogether, our results reveal that GLUT3 is a transcriptional target of ZEB1 and that this glucose transporter plays an important role in lung cancer, when tumor cells loose their epithelial characteristics to become more invasive. Moreover, these findings emphasize the development of GLUT3 inhibitory drugs as a targeted therapy for the treatment of patients with poorly differentiated tumors.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1186/2049-3002-2-11
