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

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dc.contributor.authorCreekmore, Amy L.en
dc.contributor.authorHeffron, C. Lynnen
dc.contributor.authorBrayfield, Bradley P.en
dc.contributor.authorRoberts, Paul C.en
dc.contributor.authorSchmelz, Eva M.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.contributor.departmentVirginia-Maryland College of Veterinary Medicineen
dc.date.accessed2014-01-06en
dc.date.accessioned2014-01-15T14:16:34Zen
dc.date.available2014-01-15T14:16:34Zen
dc.date.issued2013-07-16en
dc.description.abstractOvarian 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCreekmore, Amy L.; Heffron, C. L.; Brayfield, Bradley P.; Roberts, Paul C.; Schmelz, Eva M. 2013. "Regulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Cancer." Biomolecules 2013, 3(3), 386-407; doi:10.3390/biom3030386en
dc.identifier.citationCreekmore, 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.en
dc.identifier.doihttps://doi.org/10.3390/biom3030386en
dc.identifier.issn2218-273Xen
dc.identifier.urihttp://hdl.handle.net/10919/24835en
dc.identifier.urlhttp://www.mdpi.com/2218-273X/3/3/386en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectovarian canceren
dc.subjectcytoskeletonen
dc.subjectsphingosineen
dc.subjectfocal adhesionsen
dc.subjectMLCKen
dc.titleRegulation of Cytoskeleton Organization by Sphingosine in a Mouse Cell Model of Progressive Ovarian Canceren
dc.title.serialBiomoleculesen
dc.typeArticle - Refereeden
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Human Nutrition, Foods, and Exercise
Destination Area: Global Systems Science (GSS)
Journal Articles, Multidisciplinary Digital Publishing Institute (MDPI)
Scholarly Works, Biomedical Sciences and Pathobiology
Scholarly Works, Virginia-Maryland College of Veterinary Medicine