The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

Abstract

Astrocytomas are primary malignant brain tumors that originate from astrocytes. Grade IV astrocytoma or glioblastoma is a highly invasive tumor that occur within the brain parenchyma. The Rho family of small GTPases, which includes Rac1, Cdc42, and RhoA, is an important family whose members are key regulators of the invasion and migration of glioblastoma cells. In this review, we describe the role played by the Rho family of GTPases in the regulation of the invasion and migration of glioblastoma cells. Specifically, we focus on the role played by RhoA, Rac1, RhoG, and Cdc42 in cell migration through rearrangement of actin cytoskeleton, cell adhesion, and invasion. Finally, we highlight the importance of potentially targeting Rho GTPases in the treatment of glioblastoma.

TRP Channels Regulation of Rho GTPases in Brain Context and Diseases

“…TRPV1 has also been proposed as a negative prognosis marker for glioblastoma (Nabissi et al, 2016), in which invasiveness is highly dependent on RhoA activity since it regulates several matrix metalloproteinases in this type of neoplasms (Al-Koussa et al, 2020). Nevertheless, further studies are needed to detail the participation of TRPV1 in the development of neoplastic pathologies associated with neuronal or glial cells in the brain.…”

“…Moreover, upregulation of TRPC6 and subsequent increased Ca 2+ influx in podocytes lead to an aberrant activation of focal adhesion kinase (FAK), which is necessary for focal adhesion assembly and disassembly in migratory cells ( Nakuluri et al, 2019 ). RhoA activity can promote the activation of FAK ( Al-Koussa et al, 2020 ), suggesting an additional mechanism for TRPC6-RhoA mediated tumoral progress in glioma ( Figure 3 ). Although there are several possible mechanisms for TRPC6-mediated regulation of the RhoA/Rock pathway in glioma progression, this still needs to be confirmed in the context of this neoplastic disease.…”

The Role of Rho GTPases in VEGF Signaling in Cancer Cells

“…Rho GTPases are small monomeric GTP-binding proteins that were discovered in 1981. The Rho family of GTPases comprises 20 homologues of Rho whose molecular masses range between 20 and 40 kDa [15,[60][61][62].…”

“…The most studied Rho GTPases are RhoA, RhoC, RhoG, Cdc42, and Rac1. This family regulates different processes including cell growth, differentiation, apoptosis, cell cycle, and gene transcription as well as cell migration and the actin cytoskeleton [15,60,62]. Rho GTPases alternate between an active state in which they bind GTP and an inactive state in which they bind GDP [15,63,64].…”

RHOAming Through the Nucleotide Excision Repair Pathway as a Mechanism of Cellular Response Against the Effects of UV Radiation

“…Emerging as new and important regulatory components for maintaining genomic stability are the typical Rho GTPases, a small family of signaling molecules described as important regulators of cell and tissue morphology and function, acting mainly through the actin cytoskeleton. These enzymes are key mediators of diverse cellular and physiological processes such as cell division, migration and invasion (Mokady and Meiri, 2015;Al-Koussa et al, 2020). RhoA, RhoB, and RhoC isoforms comprise the Rho subfamily within the Rho GTPase family.…”