title: GLUT3 is induced during epithelial-mesenchymal transition and promotes tumor cell proliferation in non-small cell lung cancer.
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.
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Mark
authors.initials: M
authors.lastname: Masin
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Vazquez
authors.affiliation: Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
authors.forename: Simona
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Svenja
authors.initials: S
authors.lastname: Groeneveld
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Natasha
authors.initials: N
authors.lastname: Samson
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Schwalie
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Frawley
authors.affiliation: Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne 1011, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gouttenoire
authors.affiliation: Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne 1011, Switzerland.
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Trudy G
authors.initials: TG
authors.lastname: Oliver
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
authors.forename: Etienne
authors.initials: E
authors.lastname: Meylan
keywords: Epithelial-mesenchymal transition; GLUT3; Glucose transporter; Non-small cell lung cancer; SLC2A3; ZEB1
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