Inositol Phosphate Recycling Regulates Glycolytic and Lipid Metabolism That Drives Cancer Aggressiveness

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.