Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20217
Título
The antioxidant uncoupling protein 2 stimulates hnRNPA2/B1, GLUT1 and PKM2 expression and sensitizes pancreas cancer cells to glycolysis inhibition
Autor(es)
Fecha de publicación
2016-12
Cita
Brandi J, Cecconi D, Cordani M, Torrens-Mas M, Pacchiana R, Dalla Pozza E, et al. The antioxidant uncoupling protein 2 stimulates hnRNPA2/B1, GLUT1 and PKM2 expression and sensitizes pancreas cancer cells to glycolysis inhibition. Free Radic Biol Med. 2016 Dec;101:305-16.
Idioma
Inglés
Tipo de documento
research article
Resumen
Several evidence indicate that metabolic alterations play a pivotal role in cancer development. Here, we report that the mitochondrial uncoupling protein 2 (UCP2) sustains the metabolic shift from mitochondrial oxidative phosphorylation (mtOXPHOS) to glycolysis in pancreas cancer cells. Indeed, we show that UCP2 sensitizes pancreas cancer cells to the treatment with the glycolytic inhibitor 2-deoxy-D-glucose. Through a bidimensional electrophoresis analysis, we identify 19 protein species differentially expressed after treatment with the UCP2 inhibitor genipin and, by bioinformatic analyses, we show that these proteins are mainly involved in metabolic processes. In particular, we demonstrate that the antioxidant UCP2 induces the expression of hnRNPA2/B1, which is involved in the regulation of both GLUT1 and PKM2 mRNAs, and of lactate dehydrogenase (LDH) increasing the secretion of L-lactic acid. We further demonstrate that the radical scavenger N-acetyl-L-cysteine reverts hnRNPA2/B1 and PKM2 inhibition by genipin indicating a role for reactive oxygen species in the metabolic reprogramming of cancer cells mediated by UCP2. We also observe an UCP2-dependent decrease in mtOXPHOS complex I (NADH dehydrogenase), complex IV (cytochrome c oxidase), complex V (ATPase) and in mitochondrial oxygen consumption, suggesting a role for UCP2 in the counteraction of pancreatic cancer cellular respiration. All these results reveal novel mechanisms through which UCP2 promotes cancer cell proliferation with the concomitant metabolic shift from mtOXPHOS to the glycolytic pathway.
MESH
Deoxyglucose | Insulin-Secreting Cells | Mitochondria | Reactive Oxygen Species | Glycolysis | Humans | Cell Line, Tumor | Acetylcysteine | Carrier Proteins | Cell Proliferation | Membrane Proteins | RNA, Small Interfering | Thyroid Hormones | L-Lactate Dehydrogenase | Gene Expression Profiling | Glucose Transporter Type 1 | Heterogeneous-Nuclear Ribonucleoprotein Group A-B | Uncoupling Protein 2 | Signal Transduction | Oxidative Phosphorylation | RNA, Messenger | Iridoids | Gene Expression Regulation, Neoplastic
DECS
Transducción de Señal | Regulación Neoplásica de la Expresión Génica | Línea Celular Tumoral | Ribonucleoproteína Heterogénea-Nuclear Grupo A-B | Proliferación Celular | Células Secretoras de Insulina | Hormonas Tiroideas | L-Lactato Deshidrogenasa | Proteínas de la Membrana | Proteínas Portadoras | Transportador de Glucosa de Tipo 1 | Acetilcisteína | Humanos | Glucólisis | Especies Reactivas de Oxígeno | Proteína Desacopladora 2 | Desoxiglucosa | Iridoides | ARN Mensajero | ARN Interferente Pequeño | Perfilación de la Expresión Génica | Mitocondrias | Fosforilación Oxidativa
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