title: Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1.
abstract: The inositol pyrophosphates, molecular messengers containing an energetic pyrophosphate bond, impact a wide range of biologic processes. They are generated primarily by a family of three inositol hexakisphosphate kinases (IP6Ks), the principal product of which is diphosphoinositol pentakisphosphate (IP7). We report that IP6K2, via IP7 synthesis, is a major mediator of cancer cell migration and tumor metastasis in cell culture and in intact mice. IP6K2 acts by enhancing cell-matrix adhesion and decreasing cell-cell adhesion. This action is mediated by IP7-elicited nuclear sequestration and inactivation of the tumor suppressor liver kinase B1 (LKB1). Accordingly, inhibitors of IP6K2 offer promise in cancer therapy.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience.
authors.forename: Feng
authors.initials: F
authors.lastname: Rao
authors.affiliation: The Solomon H. Snyder Department of Neuroscience.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Solomon H. Snyder Department of Neuroscience.
authors.forename: Chenglai
authors.initials: C
authors.lastname: Fu
authors.affiliation: The Solomon H. Snyder Department of Neuroscience.
authors.forename: Jiyoung Y
authors.initials: JY
authors.lastname: Cha
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Department of Pharmacology and Molecular Sciences.
authors.forename: Moataz M
authors.initials: MM
authors.lastname: Gadalla
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Department of Pharmacology and Molecular Sciences.
authors.forename: Risheng
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Molecular Sciences, Lieber Institute for Brain Development, and.
authors.forename: James C
authors.initials: JC
authors.lastname: Barrow
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Department of Pharmacology and Molecular Sciences, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 ssnyder@jhmi.edu.
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007295:Inositol Phosphates; C079849:1-diphosphoinositol pentakisphosphate; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D017856:Phosphotransferases (Phosphate Group Acceptor); C099438:inositol hexakisphosphate kinase
keywords: IP6K; LKB1; cell-matrix adhesion; cell–cell adhesion; metastasis