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ACS Chem Biol. 2014 Jun 20;9(6):1340-50. doi: 10.1021/cb5001907. Epub 2014 Apr 28.

Inositol phosphate recycling regulates glycolytic and lipid metabolism that drives cancer aggressiveness.

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1
Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley , Berkeley, California 94720, United States.

Abstract

Cancer cells possess fundamentally altered metabolism that supports their pathogenic features, which includes a heightened reliance on aerobic glycolysis to provide precursors for synthesis of biomass. We show here that inositol polyphosphate phosphatase 1 (INPP1) is highly expressed in aggressive human cancer cells and primary high-grade human tumors. Inactivation of INPP1 leads to a reduction in glycolytic intermediates that feed into the synthesis of the oncogenic signaling lipid lysophosphatidic acid (LPA), which in turn impairs LPA signaling and further attenuates glycolytic metabolism in a feed-forward mechanism to impair cancer cell motility, invasiveness, and tumorigenicity. Taken together these findings reveal a novel mode of glycolytic control in cancer cells that can serve to promote key oncogenic lipid signaling pathways that drive cancer pathogenicity.

PMID:
24738946
PMCID:
PMC4076040
DOI:
10.1021/cb5001907
[Indexed for MEDLINE]
Free PMC Article

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