| Literature DB >> 24333506 |
Bassem D Khalil1, Samer Hanna1, Bechara A Saykali1, Sally El-Sitt1, Anita Nasrallah1, Daniel Marston2, Marwan El-Sabban3, Klaus M Hahn2, Marc Symons4, Mirvat El-Sibai5.
Abstract
Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility, and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Förster Resonance Energy Transfer (FRET), we show that RhoA activity localizes with focal adhesions at the basal surface of astrocytoma cells. Moreover, the knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of cells, which makes them defective in retracting their tail. This study highlights the importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and establishes StarD13 as a GAP playing a major role in this process.Entities:
Keywords: Astrocytoma; Cell motility; Rac; RhoA; StarD13
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Year: 2013 PMID: 24333506 PMCID: PMC4297755 DOI: 10.1016/j.yexcr.2013.11.023
Source DB: PubMed Journal: Exp Cell Res ISSN: 0014-4827 Impact factor: 3.905