title: The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility.
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.
authors: Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon.
authors: Bassem D
authors: BD
authors: Khalil
authors: Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon.
authors: Samer
authors: S
authors: Hanna
authors: Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon.
authors: Bechara A
authors: BA
authors: Saykali
authors: Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon.
authors: Sally
authors: S
authors: El-Sitt
authors: Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon.
authors: Anita
authors: A
authors: Nasrallah
authors: Department of Pharmacology, University of North Carolina School of Medicine, CB7365, Chapel Hill, NC27599, USA.
authors: Daniel
authors: D
authors: Marston
authors: Department of Human Morphology, Faculty of Medicine, The American University of Beirut, Beirut, Lebanon.
authors: Marwan
authors: M
authors: El-Sabban
authors: Department of Pharmacology, University of North Carolina School of Medicine, CB7365, Chapel Hill, NC27599, USA.
authors: Klaus M
authors: KM
authors: Hahn
authors: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, North Shore University Hospital, Manhasset, NY 11030, USA.
authors: Marc
authors: M
authors: Symons
authors: Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon. Electronic address: mirvat.elsibai@lau.edu.lb.
authors: Mirvat
authors: M
authors: El-Sibai
mesh_terms: D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D022001:Focal Adhesions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D034741:RNA, Small Interfering / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D034741:RNA, Small Interfering; C473607:STARD13 protein, human; D025521:Tumor Suppressor Proteins; D020742:rhoA GTP-Binding Protein
keywords: Astrocytoma; Cell motility; Rac; RhoA; StarD13