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Exp Cell Res. 2014 Feb 15;321(2):109-22. doi: 10.1016/j.yexcr.2013.11.023. Epub 2013 Dec 10.

The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility.

Author information

1
Department of Natural Sciences, The Lebanese American University, P.O. Box: 13-5053, Chouran, Beirut 1102 2801, Lebanon.
2
Department of Pharmacology, University of North Carolina School of Medicine, CB7365, Chapel Hill, NC27599, USA.
3
Department of Human Morphology, Faculty of Medicine, The American University of Beirut, Beirut, Lebanon.
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.
5
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.

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.

KEYWORDS:

Astrocytoma; Cell motility; Rac; RhoA; StarD13

PMID:
24333506
PMCID:
PMC4297755
DOI:
10.1016/j.yexcr.2013.11.023
[Indexed for MEDLINE]
Free PMC Article

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