SAICAR Stimulates Pyruvate Kinase Isoform M2 and Promotes Cancer Cell Survival in Glucose-Limited Conditions

• DOI: 10.1126/science.1224409
• Publication Date: 2012-10-20T00:50:06Z
• Authors: Kirstie E. Keller; Irene S. Tan; Young-Sam Lee
• Keywords: PKM2; Warburg Effect

Pyruvate kinase isoform M2 (PKM2) plays an important role in the growth and metabolic reprogramming of cancer cells stress conditions. Here, we report that SAICAR (succinylaminoimidazolecarboxamide ribose-5'-phosphate, intermediate de novo purine nucleotide synthesis pathway) specifically stimulates PKM2. Upon glucose starvation, cellular concentration increased oscillatory manner stimulated PKM2 activity cells. Changes amounts altered energy level, uptake, lactate production. The SAICAR-PKM2 interaction also promoted cell survival glucose-limited accumulation was not observed normal adult epithelial or lung fibroblasts, regardless This allosteric regulation may explain how coordinate different pathways to optimize their nutrient-limited conditions commonly tumor microenvironment.