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Lactate promotes glutamine uptake and metabolism in oxidative cancer cells.
Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre.
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  • Pérez-Escuredo J; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Dadhich RK; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Dhup S; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Cacace A; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Van Hée VF; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • De Saedeleer CJ; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Sboarina M; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Rodriguez F; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Fontenille MJ; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Brisson L; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Porporato PE; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
  • Sonveaux P; a From the Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School , Brussels , Belgium.
Cell Cycle ; 15(1): 72-83, 2016.
Article en En | MEDLINE | ID: mdl-26636483
Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Láctico / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Glutaminasa / Glutamina / Neoplasias Límite: Animals / Humans / Male Idioma: En Revista: Cell Cycle Año: 2016 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Láctico / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Glutaminasa / Glutamina / Neoplasias Límite: Animals / Humans / Male Idioma: En Revista: Cell Cycle Año: 2016 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos