Syndecan-2 regulation of morphology in breast carcinoma cells is dependent on RhoGTPases |
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Authors: | Hooi Ching Lim John R Couchman |
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Institution: | Department of Biomedical Sciences, University of Copenhagen, Denmark |
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Abstract: | BackgroundWhile syndecan-2 is usually considered a mesenchymal transmembrane proteoglycan, it can be upregulated in some tumour cells, such as the malignant breast carcinoma cell line, MDA-MB231. Depletion of this syndecan by siRNA, but not other syndecans, has a marked effect on cell morphology, increasing spreading, microfilament bundle and focal adhesion formation, with reduced cell migration.MethodsA combination of siRNA transfection, immunofluorescence microscopy, phosphoprotein analysis and migration assays was used to determine how syndecan-2 may influence the cytoskeleton.ResultsThe altered adhesion upon syndecan-2 depletion was dependent on the RhoGTPases. p190ARhoGAP relocated to the margins of spreading cells, where it codistributed with syndecan-4 and active β1-integrin. This was accompanied by increased RhoGAP tyrosine phosphorylation, indicative of activity and RhoGTPase suppression. Consistent with this, GTP-RhoA was strongly present at the edges of control cells, but lost after syndecan-2 reduction by siRNA treatments. Further, RhoA, but not RhoC was shown to be essential for the anchored phenotype of these breast carcinoma cells that accompanied siRNA-mediated loss of syndecan-2.ConclusionsSyndecan-2 has a key role in promoting the invasive activity of these cells, in part by regulating the RhoGTPases.General significanceSyndecan-2, as a cell surface receptor is accessible for targeting to determine whether breast tumour progression is altered. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. |
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Keywords: | Heparan sulfate Proteoglycan Cytoskeleton Cell adhesion RhoGAP RhoGTPases |
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