PI3K/AKT/Afadin signaling pathway contributes to pathological vascularization in glioblastomas.

Abstract

Glioblastomas are brain tumors with extensive vascularization that are associated with tumor malignancy. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is activated in endothelial cell tumors, although its exact function in glioblastoma neovascularization is poorly characterized. The present study identified that endothelial cells derived from human glioblastomas exhibit increased permeability and motility compared with normal brain vascular endothelial cells. Furthermore, the phosphorylation of AKT was significantly induced in glioblastoma-derived endothelial cells and glioblastoma vessels. To the best of our knowledge, the present study demonstrated for the first time that the cell-cell adhesion junction protein Afadin is phosphorylated and re-localized in glioblastoma-derived endothelial cells, and the phosphorylation and re-localization of Afadin is PI3K/AKT pathway-dependent. AKT-mediated phosphorylation and re-localization of Afadin may be critically involved in the modulation of brain endothelial permeability and migration. Therapies targeting the PI3K/AKT/Afadin pathway may therefore be beneficial for reducing the angiogenic potential of glioblastoma.