Rho GTPases in primary brain tumor malignancy and invasion

Abstract

Gliomas are the most common type of malignant primary brain tumor in humans, accounting for 80 % of malignant cases. Expression and activity of Rho GTPases, which coordinate several cellular processes including cellcycle progression and cell migration, are commonly altered in many types of primary brain tumor. Here we review the suggested effects of deregulated Rho GTPase signaling on brain tumor malignancy, highlighting the controversy in the field. For instance, whereas expression of RhoA and RhoB has been found to be significantly reduced in astrocytic tumors, other studies have reported Rho-dependent LPAinduced migration in glioma cells. Moreover, whereas the Rac1 expression level has been found to be reduced in astrocytic tumor, it was overexpressed and induced invasion in medulloblastoma tumors. In addition to the Rho GTPases themselves, several of their downstream effectors (including ROCK, mDia, and N-WASP) and upstream regulators (including GEFs, GAPs, PI3K, and PTEN) have also been implicated in primary brain tumors.