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

Kirstie E. Keller, Irene S. Tan, Young Sam Lee

Research output: Contribution to journalArticlepeer-review

173 Scopus citations

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.

Original languageEnglish
Pages (from-to)1069-1072
Number of pages4
JournalScience
Volume338
Issue number6110
DOIs
StatePublished - Nov 23 2012

ASJC Scopus subject areas

  • General

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