Proceedings of the National Academy of Sciences · 2015 · 97 citations · 36 references
MedicineCancer BiologyOncologyEnzymologyMetastasisSignal TransductionCancer Cell SignalingMetastatic Signaling PathwaysOncogenic Signaling PathwaysProtein Kinase CascadesCancer Cell MigrationCancer Cell-cell AdhesionCell-cell Adhesion ComplexesEnzymesInositol Phosphate SignalingInositol Triphosphate SignalingKinase Signaling InhibitorsTumor Metastasis Biology
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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Structure-based prediction of protein–protein interactions on a genome-wide scale
Qiangfeng Cliff Zhang, Donald Petrey, Lei Deng et al. · Nature · 2012 · 746 citations