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• W2003170155 abstract "The serine protease urokinase-type plasminogen activator (uPA) plays a significant role in tumor cell invasion and metastasis when bound to its specific receptor, uPAR (also known as CD87). In addition to the uPA-uPAR system, matrix metalloproteinases (MMPs) are involved in tumor cell invasion and metastasis. In this study, we achieved specific inhibition of uPAR and MMP-9 using RNAi technology. We introduced small interfering RNA to downregulate the expression of uPAR and MMP-9 (pUM) in breast cancer cell lines (MDA MB 231 and ZR 75 1). In vitro angiogenesis studies indicated a decrease in the angiogenic potential of the treated cells; in particular, a remarkable decrease was observed in the cells treated with bicistronic construct (pUM) in comparision to the controls. Additionally, bicistronic construct inhibited the formation of capillary-like structures in in vivo models of angiogenesis. Similarly, the invasive potential and migration decreased dramatically when treated with the bicistronic construct as shown by matrigel invasion and migration assays. These results suggest a synergistic effect from the simultaneous downregulation of uPAR and MMP-9. We also assessed the levels of phosphorylated forms of MAPK, ERK and AKT signaling pathway molecules and found reduction in the levels of these molecules in cells treated with the bicistronic construct as compared to the control cells. Furthermore, targeting both uPAR and MMP-9 totally regressed orthotopic breast tumors in nude mice. In conclusion, our results provide evidence that the simultaneous downregulation of uPAR and MMP-9 using RNAi technology may provide an effective tool for breast cancer therapy." @default.
• W2003170155 created "2016-06-24" @default.
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• W2003170155 creator A5063197597 @default.
• W2003170155 creator A5071514249 @default.
• W2003170155 date "2007-07-26" @default.
• W2003170155 modified "2023-10-13" @default.
• W2003170155 title "<i>Retracted</i>: RNAi‐mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease‐9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth" @default.
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• W2003170155 doi "https://doi.org/10.1002/ijc.22962" @default.
• W2003170155 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2396459" @default.
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