Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1.
basic_science · Level V
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- Record sourced from PubMed, PMID 25617365.
- Also identified by DOI 10.1073/pnas.1424642112 and PMC identifier 4330756.
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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.
Medical subject headings
- Cell Adhesion
- Cell Movement
- Inositol Phosphates
- Neoplasm Metastasis
- Phosphotransferases (Phosphate Group Acceptor)
- Protein Serine-Threonine Kinases