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• W1989329686 abstract "The stromal cell-derived factor-1 (SDF-1)/CXC receptor 4 (CXCR4) axis has been shown to play a role in colorectal cancer progression. In addition, the protease urokinase-type plasminogen activator (uPA) is an important factor in tumor cell invasion and metastasis. However, the mechanism by which SDF-1 mediates uPA expression in human colorectal cancer cells remains unknown. We investigated the molecular mechanism governing the interaction between SDF-1 stimulation and uPA expression in three human colon cancer cell lines (DLD-1, SW48, and COLO 205). We found that SDF-1 stimulation led to an increase in the expression and secretion of uPA in these cells. Experiments involving specific inhibitors and small interfering RNA demonstrated that the activation of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways are critical for SDF-1-induced uPA expression. Analysis of transcription factor binding using ELISA and chromatin immunoprecipitation assays revealed that SDF-1 increased Sp1- and AP-1-DNA-binding activities in DLD-1 cells. Inhibition of Sp1 and AP-1 activation blocked the SDF-1-induced expression and activity of the uPA promoter. The effect of SDF-1 on DLD-1 signaling and uPA expression was mediated by the CXCR4/β1 integrin axis. In summary, our findings elucidate the mechanisms of SDF-1/CXCR4 downstream signaling and provide insights into the function of SDF-1 in colon cancer cells. J. Cell. Physiol. 227: 1114–1122, 2012. © 2011 Wiley Periodicals, Inc." @default.
• W1989329686 created "2016-06-24" @default.
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• W1989329686 date "2011-12-22" @default.
• W1989329686 modified "2023-10-16" @default.
• W1989329686 title "Stromal cell-derived factor-1/CXC receptor 4 and β1 integrin interaction regulates urokinase-type plasminogen activator expression in human colorectal cancer cells" @default.
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• W1989329686 doi "https://doi.org/10.1002/jcp.22831" @default.
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