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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.

SUBMITTER: Rao F

PROVIDER: S-EPMC4330756 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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

Rao Feng F Xu Jing J Fu Chenglai C Cha Jiyoung Y JY Gadalla Moataz M MM Xu Risheng R Barrow James C JC Snyder Solomon H SH

Proceedings of the National Academy of Sciences of the United States of America 20150123 6

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 d ...[more]

PMID: 25617365

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