Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1
Menée sur des lignées cellulaires et des modèles murins, cette étude met en évidence des mécanismes par lesquels, en inactivant le suppresseur de tumeurs LKB1, la kinase IP6K2 favorise le processus métastatique
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.