Lactate Reprograms Energy and Lipid Metabolism in Glucose-Deprived Oxidative Glioma Stem Cells.

摘要: Fast-growing tumors satisfy their bioenergetic needs by supplementing glucose with alternative carbon sources. Cancer stem cells are the most versatile and robust within malignant tumors. They avoid potentially lethal metabolic other types of stress through flexible reprogramming relevant pathways, but it has remained unclear whether sources important for maintenance tumor-propagating ability. Here we assessed ability glycolytic oxidative murine glioma (GSCs) to grow in an ultralow medium. Sphere formation assays revealed that exogenous lactate acetate reversed growth impairment GSCs such Extracellular flux analysis showed supported oxygen consumption these cells, whereas metabolomics increased intracellular levels tricarboxylic acid cycle intermediates, ATP, GTP as well adenylate guanylate charge. Lactate also depletion choline apparent glucose-deprived reprogrammed phospholipid fatty biosynthesis. This was associated a more aggressive phenotype intracranial formed lactate-treated GSCs. Our results thus suggest is energetic biosynthetic substrate GSCs, sustains under conditions deprivation.