Ras-oncogenic pathway contributes to the pathogenesis of various tumours in humans, in which mutations of three canonical genes including H-Ras, N-Ras and K-Ras are the most common events. Dysregulation of Ras signalling can be tumourigenic, especially
gliomas of the central nervous system. Rap
proteins are members of the
small GTPase superfamily that involved in many biological processes. However, it remains largely unclear as to whether and how Rap
proteins are involved in the development of multiple
gliomas. We found that the levels of the
protein Rap2a and the activity of Rap2a (GTP-Rap2a) were weakly expressed in
glioma tissues. Overexpressed Rap2a significantly inhibited the migration and invasion of
glioma cells with an increase of GTP-Rap2a. Overexpression of the dominant-active (DA-Rap2a), but not the dominant-negative (DN-Rap2a) form of Rap2a, also similarly inhibited the migration and invasion of
glioma cells by reducing the phosphorylation level of AKT. In contrast, downregulation of Rap2a promoted
glioma migration and invasion, and raised the phosphorylation level of AKT, whereas these effects were inhibited by PI3K-specific inhibitor,
LY294002. Thus unlike the other family members of Ras, Rab2a probably serves as a tumour suppressor in the pathogenesis of
glioma.