dc.contributor.author | Gkretsi, Vasiliki | en |
dc.contributor.author | Kalli, Maria | en |
dc.contributor.author | Efstathiades, Christodoulos | en |
dc.contributor.author | Papageorgis, Panagiotis | en |
dc.contributor.author | Papanikolaou, Vassilios | en |
dc.contributor.author | Zacharia, Lefteris C. | en |
dc.contributor.author | Tsezou, Aspasia | en |
dc.contributor.author | Athanassiou, Evangelos | en |
dc.contributor.author | Stylianopoulos, Triantafyllos | en |
dc.creator | Gkretsi, Vasiliki | en |
dc.creator | Kalli, Maria | en |
dc.creator | Efstathiades, Christodoulos | en |
dc.creator | Papageorgis, Panagiotis | en |
dc.creator | Papanikolaou, Vassilios | en |
dc.creator | Zacharia, Lefteris C. | en |
dc.creator | Tsezou, Aspasia | en |
dc.creator | Athanassiou, Evangelos | en |
dc.creator | Stylianopoulos, Triantafyllos | en |
dc.date.accessioned | 2021-01-27T10:17:51Z | |
dc.date.available | 2021-01-27T10:17:51Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/63819 | |
dc.description.abstract | Extracellular 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.language.iso | en | en |
dc.source | Scientific Reports | en |
dc.source.uri | https://www.nature.com/articles/s41598-019-46575-0 | |
dc.title | Depletion of Ras Suppressor-1 (RSU-1) promotes cell invasion of breast cancer cells through a compensatory upregulation of a truncated isoform | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1038/s41598-019-46575-0 | |
dc.description.volume | 9 | |
dc.description.issue | 1 | |
dc.author.faculty | Πολυτεχνική Σχολή / Faculty of Engineering | |
dc.author.department | Τμήμα Μηχανικών Μηχανολογίας και Κατασκευαστικής / Department of Mechanical and Manufacturing Engineering | |
dc.type.uhtype | Article | en |
dc.contributor.orcid | Stylianopoulos, Triantafyllos [0000-0002-3093-1696] | |
dc.contributor.orcid | Papageorgis, Panagiotis [0000-0002-7595-5616] | |
dc.contributor.orcid | Gkretsi, Vasiliki [0000-0002-3671-4078] | |
dc.contributor.orcid | Zacharia, Lefteris C. [0000-0002-0327-2373] | |
dc.gnosis.orcid | 0000-0002-3093-1696 | |
dc.gnosis.orcid | 0000-0002-7595-5616 | |
dc.gnosis.orcid | 0000-0002-3671-4078 | |
dc.gnosis.orcid | 0000-0002-0327-2373 | |