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

Rao, Feng; Xu, Jing; Fu, Chenglai; Cha, Jiyoung Y; Gadalla, Moataz M; Xu, Risheng; Barrow, James C; Snyder, Solomon H · Proc Natl Acad Sci U S A · 2015

basic_science · Level V

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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.

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