title: Loss of GLUT4 induces metabolic reprogramming and impairs viability of breast cancer cells.
abstract: Metabolic reprogramming strategies focus on the normalization of metabolism of cancer cells and constitute promising targets for cancer treatment. Here, we demonstrate that the glucose transporter 4 (GLUT4) has a prominent role in basal glucose uptake in MCF7 and MDA-MB-231 breast cancer cells. We show that shRNA-mediated down-regulation of GLUT4 diminishes glucose uptake and induces metabolic reprogramming by reallocating metabolic flux to oxidative phosphorylation. This reallocation is reflected on an increased activity of the mitochondrial oxidation of pyruvate and lower lactate release. Altogether, GLUT4 inhibition compromises cell proliferation and critically affects cell viability under hypoxic conditions, providing proof-of-principle for the feasibility of using pharmacological approaches to inhibit GLUT4 in order to induce metabolic reprogramming in vivo in breast cancer models.
authors.affiliation: Departamento de Biología Funcional, Área de Fisiología, Universidad de Oviedo, c/ Julian Claveria s/n, Oviedo, 33006, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garrido
authors.forename: Fernando G
authors.initials: FG
authors.lastname: Osorio
authors.forename: Javier
authors.initials: J
authors.lastname: Morán
authors.forename: Estefanía
authors.initials: E
authors.lastname: Cabello
authors.forename: Ana
authors.initials: A
authors.lastname: Alonso
authors.forename: José M P
authors.initials: JM
authors.lastname: Freije
authors.forename: Celestino
authors.initials: C
authors.lastname: González
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics*; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D005947:Glucose; D051275:Glucose Transporter Type 4; D019344:Lactic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019289:Pyruvic Acid; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C495692:SLC2A4 protein, human; C546842:MTOR protein, human