The regulation of Rhoa in focal adhesions by starD13 is essential for astrocytoma cell motility. (c2011)

Abstract

Malignant astrocytomas are associated with poor prognosis and high morbidity and mortality rates despite intensive treatment. These tumors rarely metastasize into distant regions of the body; however, they are highly invasive into adjacent and distant regions of the normal brain, which renders them surgically and medically unmanageable and accounts for their fatal outcome. Invasion is a multistep process, which ultimately requires the cell to actively migrate through the ECM. Proper cell adhesion dynamics, involving the assembly and the disassembly of adhesion, is essential for the completion of the motility cycle. Rho-GTPases, mainly RhoA, Rac, and Cdc42, play a major role in the regulation of the processes that ultimately lead to cell migration. StarD13 is a RhoGAP that inhibits the function of RhoA and Cdc42. We first aimed at determining the role of RhoA in the progression of astrocytic tumors, a topic that is still controversial in the literature. Our results showed that RhoA plays a positive role in this aspect. Our current study also investigates the roles of RhoA, Rac1, and StarD13 in cell adhesion and cell migration. Our results showed that RhoA, Rac1, and StarD13 are essential for astrocytoma cell migration. Rac1 plays a role in the formation of focal complexes, which ultimately mature into focal adhesions under the action of RhoA. StarD13 plays a role in the inhibition of RhoA in focal complexes, a process that seems indispensible for astrocytoma cell migration.