SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions.

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

SUBMITTER: Keller KE 

PROVIDER: S-EPMC3527123 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature