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dc.contributor.authorGkretsi, Vasilikien
dc.contributor.authorKalli, Mariaen
dc.contributor.authorEfstathiades, Christodoulosen
dc.contributor.authorPapageorgis, Panagiotisen
dc.contributor.authorPapanikolaou, Vassiliosen
dc.contributor.authorZacharia, Lefteris C.en
dc.contributor.authorTsezou, Aspasiaen
dc.contributor.authorAthanassiou, Evangelosen
dc.contributor.authorStylianopoulos, Triantafyllosen
dc.creatorGkretsi, Vasilikien
dc.creatorKalli, Mariaen
dc.creatorEfstathiades, Christodoulosen
dc.creatorPapageorgis, Panagiotisen
dc.creatorPapanikolaou, Vassiliosen
dc.creatorZacharia, Lefteris C.en
dc.creatorTsezou, Aspasiaen
dc.creatorAthanassiou, Evangelosen
dc.creatorStylianopoulos, Triantafyllosen
dc.description.abstractExtracellular matrix (ECM)-adhesion proteins and actin cytoskeleton are pivotal in cancer cell invasion. Ras Suppressor-1 (RSU-1), a cell-ECM adhesion protein that interacts with PINCH-1, thus being connected to Integrin Linked Kinase (ILK), alpha-parvin (PARVA), and actin cytoskeleton, is up-regulated in metastatic breast cancer (BC) samples. Apart from the originally-identified gene (RSU-1L), an alternatively-spliced isoform (RSU-1-X1) has been reported. We used non-invasive MCF-7 cells, expressing only RSU-1L, and highly invasive MDA-MB-231-LM2 expressing both isoforms and generated stable shRNA-transduced cells lacking RSU-1L, while the truncated RSU-1-X1 isoform was depleted by siRNA-mediated silencing. RSU-1L depletion in MCF-7 cells resulted in complete abrogation of tumor spheroid invasion in three-dimensional collagen gels, whereas it promoted MDA-MB-231-LM2 invasion, through a compensatory upregulation of RSU-1-X1. When RSU-1-X1 was also eliminated, RSU-1L-depletion-induced migration and invasion were drastically reduced being accompanied by reduced urokinase plasminogen activator expression. Protein expression analysis in 23 human BC samples corroborated our findings showing RSU-1L to be upregulated and RSU-1-X1 downregulated in metastatic samples. We demonstrate for the first time, that both RSU-1 isoforms promote invasion in vitro while RSU-1L elimination induces RSU-1-X1 upregulation to compensate for the loss. Hence, we propose that both isoforms should be blocked to effectively eliminate metastasis.en
dc.sourceScientific Reportsen
dc.titleDepletion of Ras Suppressor-1 (RSU-1) promotes cell invasion of breast cancer cells through a compensatory upregulation of a truncated isoformen
dc.description.issue1Πολυτεχνική Σχολή / Faculty of EngineeringΤμήμα Μηχανικών Μηχανολογίας και Κατασκευαστικής / Department of Mechanical and Manufacturing Engineering
dc.contributor.orcidStylianopoulos, Triantafyllos [0000-0002-3093-1696]
dc.contributor.orcidPapageorgis, Panagiotis [0000-0002-7595-5616]
dc.contributor.orcidGkretsi, Vasiliki [0000-0002-3671-4078]
dc.contributor.orcidZacharia, Lefteris C. [0000-0002-0327-2373]

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