Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1

Feng Rao, Jing Xu, Chenglai Fu, Jiyoung Y. Cha, Moataz M. Gadalla, Risheng Xu, James C. Barrow, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1773-1778
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number6
DOIs
StatePublished - Feb 10 2015

Keywords

  • Cell-cell adhesion
  • Cell-matrix adhesion
  • IP6K
  • LKB1
  • Metastasis

ASJC Scopus subject areas

  • General

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