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Science 338 (6110): 1069-1072

Copyright © 2012 by the American Association for the Advancement of Science

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

Kirstie E. Keller,1 Irene S. Tan,2 Young-Sam Lee1,*

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.

1 Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
2 National Institutes of Health–Johns Hopkins University Graduate Partnerships Program, Baltimore, MD 21218, USA.

* To whom correspondence should be addressed. E-mail: ylee99{at}jhu.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Allosteric Regulation of PKM2 Allows Cellular Adaptation to Different Physiological States.
D. Y. Gui, C. A. Lewis, and M. G. Vander Heiden (2013)
Science Signaling 6, pe7
   Abstract »    Full Text »    PDF »
Dual roles of PKM2 in cancer metabolism.
S. Wu and H. Le (2013)
Acta Biochim Biophys Sin 45, 27-35
   Abstract »    Full Text »    PDF »

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