Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells.

摘要: Background Aerobic glycolysis, discovered by Otto Warburg, is a hallmark of cancer metabolism even though not yet fully understood. The low activity the cancerous pyruvate kinase isozyme (M2) thought to play an important role facilitating conversion glycolytic intermediates other anabolic pathways support tumors' high proliferation rate. Methods Five breast cell lines representing different molecular subtypes were used in this study where real time measurements cellular bioenergetics and immunoblotting analysis energy- nutrient-sensing employed investigate potential effects PKM2 allosteric activator (DASA-58) glucose rewiring. Results In study, we show that DASA-58 can induce cells without affecting overall survival. drug also able reduce TXNIP levels (an intracellular sensor) probably through depletion upstream metabolites independent AMPK ER signaling. shows induction phosphorylation (T172) response treatment effect be potentiated combining with metabolic inhibitors. Conclusions Altogether, multifaceted reprogramming induced increases their susceptibility therapeutics suggesting suitability sensor as marker PK activity.