The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility |
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Authors: | Bassem D. Khalil Samer Hanna Bechara A. Saykali Sally El-Sitt Anita Nasrallah Daniel Marston Marwan El-Sabban Klaus M. Hahn Marc Symons Mirvat El-Sibai |
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Affiliation: | 1. Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon;2. Department of Human Morphology, Faculty of Medicine, The American University of Beirut, Beirut, Lebanon;3. Department of Pharmacology, University of North Carolina School of Medicine, CB7365, Chapel Hill, NC27599, USA;4. Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, North Shore University Hospital, Manhasset, NY 11030, USA |
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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. |
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Keywords: | StarD13 RhoA Rac Astrocytoma Cell motility |
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