title: Inositol phosphate recycling regulates glycolytic and lipid metabolism that drives cancer aggressiveness.
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.
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Benjamin
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Louie
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Mulvihill
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Kohnz
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Li
authors.forename: Lauryn G
authors.initials: LG
authors.lastname: Chan
authors.forename: Antonio
authors.initials: A
authors.lastname: Sorrentino
authors.forename: Sourav
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Alyssa
authors.initials: A
authors.lastname: Cozzo
authors.forename: Anayo
authors.initials: A
authors.lastname: Ohiri
authors.forename: Andrei
authors.initials: A
authors.lastname: Goga
authors.forename: Shu-Wing
authors.initials: SW
authors.lastname: Ng
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D055442:Metabolome / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D007295:Inositol Phosphates; D034741:RNA, Small Interfering; D010744:Phosphoric Monoester Hydrolases; C053087:inositol-1,4-bisphosphate 1-phosphatase
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