Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

Autor: Vincent F. Van Hée, Paolo E. Porporato, Lucie Brisson, Fabien Rodriguez, Jhudit Pérez-Escuredo, Andrea Cacace, Suveera Dhup, Marie-Joséphine Fontenille, Pierre Sonveaux, Christophe De Saedeleer, Martina Sboarina, Rajesh Kumar Dadhich
Přispěvatelé: Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut de Recherche Expérimentale et Clinique (IREC)
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
[SDV]Life Sciences [q-bio]
Glutamine
Nude
Mice
Neoplasms
Basic Helix-Loop-Helix Transcription Factors
Glycolysis
Inbred BALB C
ComputingMilieux_MISCELLANEOUS
Cancer
Mice
Inbred BALB C
C-Myc
Glutaminolysis
Hypoxia-inducible factor (HIF)
Hypoxiainducible factor-2 (HIF-2)
Lactate signaling
Monocarboxylate transporter 1 (MCT1)
Tumor metabolism
Animals
Glutaminase
HeLa Cells
Humans
Lactic Acid
Mice
Nude
Monocarboxylic Acid Transporters
Oxidation-Reduction
Symporters
Molecular Biology
Developmental Biology
Cell Biology
Cell biology
Monocarboxylate transporter 1
Biochemistry
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Oxidative phosphorylation
Biology
03 medical and health sciences
Report
Catabolism
Metabolism
030104 developmental biology
biology.protein
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Zdroj: Cell Cycle
Cell Cycle, Taylor & Francis, 2016, 15 (1), pp.72-83. ⟨10.1080/15384101.2015.1120930⟩
ISSN: 1551-4005
1538-4101
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: