dc.creator | Gkretsi V., Kalli M., Efstathiades C., Papageorgis P., Papanikolaou V., Zacharia L.C., Tsezou A., Athanassiou E., Stylianopoulos T. | en |
dc.date.accessioned | 2023-01-31T07:43:16Z | |
dc.date.available | 2023-01-31T07:43:16Z | |
dc.date.issued | 2019 | |
dc.identifier | 10.1038/s41598-019-46575-0 | |
dc.identifier.issn | 20452322 | |
dc.identifier.uri | http://hdl.handle.net/11615/72536 | |
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. © 2019, The Author(s). | en |
dc.language.iso | en | en |
dc.source | Scientific Reports | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068892233&doi=10.1038%2fs41598-019-46575-0&partnerID=40&md5=b98a0fe02a4467366343bae587e7a7af | |
dc.subject | isoprotein | en |
dc.subject | LIM protein | en |
dc.subject | LIMS1 protein, human | en |
dc.subject | membrane protein | en |
dc.subject | RSU1 protein, human | en |
dc.subject | signal transducing adaptor protein | en |
dc.subject | small interfering RNA | en |
dc.subject | transcription factor | en |
dc.subject | urokinase | en |
dc.subject | actin filament | en |
dc.subject | breast tumor | en |
dc.subject | cell motion | en |
dc.subject | extracellular matrix | en |
dc.subject | genetics | en |
dc.subject | human | en |
dc.subject | MCF-7 cell line | en |
dc.subject | metabolism | en |
dc.subject | metastasis | en |
dc.subject | molecularly targeted therapy | en |
dc.subject | pathology | en |
dc.subject | tumor invasion | en |
dc.subject | upregulation | en |
dc.subject | Actin Cytoskeleton | en |
dc.subject | Adaptor Proteins, Signal Transducing | en |
dc.subject | Breast Neoplasms | en |
dc.subject | Cell Movement | en |
dc.subject | Extracellular Matrix | en |
dc.subject | Humans | en |
dc.subject | LIM Domain Proteins | en |
dc.subject | MCF-7 Cells | en |
dc.subject | Membrane Proteins | en |
dc.subject | Molecular Targeted Therapy | en |
dc.subject | Neoplasm Invasiveness | en |
dc.subject | Neoplasm Metastasis | en |
dc.subject | Protein Isoforms | en |
dc.subject | RNA, Small Interfering | en |
dc.subject | Transcription Factors | en |
dc.subject | Up-Regulation | en |
dc.subject | Urokinase-Type Plasminogen Activator | en |
dc.subject | Nature Publishing Group | en |
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 | journalArticle | en |