title: PTEN regulates plasma membrane expression of glucose transporter 1 and glucose uptake in thyroid cancer cells.
abstract: Glucose represents an important source of energy for the cells. Proliferating cancer cells consume elevated quantity of glucose, which is converted into lactate regardless of the presence of oxygen. This phenomenon, known as the Warburg effect, has been proven to be useful for imaging metabolically active tumours in cancer patients by (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glucose is internalised in the cells by glucose transporters (GLUTs) belonging to the GLUT family. GLUT1 (SLC2A1) is the most prevalent isoform in more aggressive and less differentiated thyroid cancer histotypes. In a previous work, we found that loss of expression of PTEN was associated with increased expression of GLUT1 on the plasma membrane (PM) and probability of detecting thyroid incidentalomas by FDG-PET. Herein, we investigated the molecular pathways that govern the expression of GLUT1 on the PM and the glucose uptake in WRO (expressing WT PTEN) and FTC133 (PTEN null) follicular thyroid cancer cells cultured under glucose-depleted conditions. The membrane expression of GLUT1 was enhanced in glucose-deprived cells. Through genetic manipulations of PTEN expression, we could demonstrate that the lack of this oncosuppressor has a dominant effect on the membrane expression of GLUT1 and glucose uptake. We conclude that loss of function of PTEN increases the probability of cancer detection by FDG-PET or other glucose-based imaging diagnosis.
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Morani
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Suratchanee
authors.initials: S
authors.lastname: Phadngam
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Follo
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Titone
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Aimaretti
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galetto
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Alabiso
authors.affiliation: Laboratory of Molecular Pathology and NanobioimagingDepartment of Health SciencesUnit of Clinical EndocrinologyUnit of OncologyDepartment of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Via Solaroli 17, 28100 Novara, Italy isidoro@med.unipmn.it.
authors.forename: Ciro
authors.initials: C
authors.lastname: Isidoro
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D005947:Glucose
keywords: FDG–PET imaging, cancer; GLUT; PTEN; Warburg effect; glucose