title: 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 allosteric regulation may explain how cancer cells coordinate different metabolic pathways to optimize their growth in the nutrient-limited conditions commonly observed in the tumor microenvironment.
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Kirstie E
authors.initials: KE
authors.lastname: Keller
authors.forename: Irene S
authors.initials: IS
authors.lastname: Tan
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000494:Allosteric Regulation; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011770:Pyruvate Kinase / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012263:Ribonucleosides / Q000378:metabolism* / Q000494:pharmacology; D059016:Tumor Microenvironment
chemical_list: D011994:Recombinant Proteins; D012263:Ribonucleosides; C043566:succinylaminoimidazole carboxamide riboside; D000620:Aminoimidazole Carboxamide; D011770:Pyruvate Kinase; D005947:Glucose