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Biomolecules 2013, 3(3), 386-407;

Regulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Cancer

Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA 24061, USA
Department of Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA
Authors to whom correspondence should be addressed.
Received: 3 June 2013 / Revised: 4 July 2013 / Accepted: 8 July 2013 / Published: 16 July 2013
(This article belongs to the Special Issue Sphingolipids and Bioactive Lipids)
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Ovarian cancer is a multigenic disease and molecular events driving ovarian cancer progression are not well established. We have previously reported the dysregulation of the cytoskeleton during ovarian cancer progression in a syngeneic mouse cell model for progressive ovarian cancer. In the present studies, we investigated if the cytoskeleton organization is a potential target for chemopreventive treatment with the bioactive sphingolipid metabolite sphingosine. Long-term treatment with non-toxic concentrations of sphingosine but not other sphingolipid metabolites led to a partial reversal of a cytoskeleton architecture commonly associated with aggressive cancer phenotypes towards an organization reminiscent of non-malignant cell phenotypes. This was evident by increased F-actin polymerization and organization, a reduced focal adhesion kinase expression, increased a-actinin and vinculin levels which together led to the assembly of more mature focal adhesions. Downstream focal adhesion signaling, the suppression of myosin light chain kinase expression and hypophosphorylation of its targets were observed after treatment with sphingosine. These results suggest that sphingosine modulate the assembly of actin stress fibers via regulation of focal adhesions and myosin light chain kinase. The impact of these events on suppression of ovarian cancer by exogenous sphingosine and their potential as molecular markers for treatment efficacy warrants further investigation. View Full-Text
Keywords: ovarian cancer; cytoskeleton; sphingosine; focal adhesions; MLCK ovarian cancer; cytoskeleton; sphingosine; focal adhesions; MLCK

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Creekmore, A.L.; Heffron, C.L.; Brayfield, B.P.; Roberts, P.C.; Schmelz, E.M. Regulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Cancer. Biomolecules 2013, 3, 386-407.

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