Benjamin, Daniel I.Louie, Sharon M.Mulvihill, Melinda M.Kohnz, Rebecca A.Li, Daniel S.Chan, Lauryn G.Sorrentino, AntonioBandyopadhyay, SouravCozzo, AlyssaOhiri, AnayoGoga, AndreiNg, Shu-WingNomura, Daniel K.2015-05-042014Benjamin, D., S. M. Louie, M. M. Mulvihill, R. A. Kohnz, D. S. Li, L. G. Chan, A. Sorrentino, et al. 2014. “Inositol Phosphate Recycling Regulates Glycolytic and Lipid Metabolism That Drives Cancer Aggressiveness.” ACS Chemical Biology 9 (6): 1340-1350. doi:10.1021/cb5001907. http://dx.doi.org/10.1021/cb5001907.1554-8929http://nrs.harvard.edu/urn-3:HUL.InstRepos:15034927Cancer 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.en-USArticlesJournal Article2015-05-0410.1021/cb5001907