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 cell-cycle 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 LPA-induced 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.

Gene expression changes in rat brain after short and long exposures to particulate matter in Los Angeles basin air: Comparison with human brain tumors

“…6). This pattern of expression agrees with the data obtained on other tumors where Rac1 gene was expressed as part of proliferation and tumor invasion pathways (Chan et al, 2005;Khalil and El-Sibai, 2012). Table 4 Arc and Rac1 expression in normal human brain and brain tumors.…”

“…These genes were: Ras-related Rac1 (Entrez Gene: 363875), placenta-specific 8/onzin (Entrez Gene: 360914), and calmodulin 3 (Entrez Gene: 24244). Rac1 has been implicated in brain tumor invasion (Chan et al, 2005;Khalil and El-Sibai, 2012), onzin can affect proliferation, apoptosis, and cell transformation (Li et al, 2006;Rogulski et al, 2005), and calmodulin 3 (genetic variant of calmodulin) plays important roles in Ca 2+ -dependent regulation of cell proliferation and is often increased in tumor cells (Prostko et al, 1997).…”

Cholesterol 24S-Hydroxylase Overexpression Inhibits the Liver X Receptor (LXR) Pathway by Activating Small Guanosine Triphosphate-Binding Proteins (sGTPases) in Neuronal Cells

“…In accordance to their pivotal role in the CNS, Ras, Rho, and Rab sGTPases have also been implicated in a number of neurological diseases. These diseases range from genetic defects such as X-linked non-specific mental retardation, Niemann-Pick disease Type C or choroideremia to sporadic neurological disorders such as late-onset AD, Parkinson's disease, multiple sclerosis, brain tumors, or even brain disorders resulting from ischemic stroke [10,30,[36][37][38][39][40][41][42].…”

Glioma cell migration and invasion as potential target for novel treatment strategies

“…Rho, Rac or CDC42 are highly expressed, and expression often correlates with poor clinical outcome [119][120][121]. In several preclinical investigations, the inhibition of small GTPase was associated with a significantly decreased migratory-invasive potential of glioma cell and could therefore constitute a target for future glioma treatment strategies [122].…”