5-Lipoxygenase and cysteinyl leukotriene receptor 1 regulate epidermal growth factor-induced cell migration through Tiam1 upregulation and Rac1 activation.
Bottom Line: In this study, we found that 5-lipoxygenase (5-LOX) is activated in the process of EGF-induced cell migration, and that leukotriene C4 (LTC4 ) produced by 5-LOX mediated the second wave of Rac1 activation, as well as cell migration.Furthermore, these effects caused by LTC4 were found to be blocked in the presence of the antagonist of cysteinyl leukotriene receptor 1 (CysLT1).We also found that 5-LOX inhibitors, CysLT1 antagonists and the knockdown of CysLT1 inhibited EGF-induced T cell lymphoma invasion and metastasis-inducing protein 1 (Tiam1) expression.
Affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.Show MeSH
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Mentions: Finally, we confirmed the involvement of CysLT1 signaling in EGF-induced Tiam1 expression by using RNAi experiments. The successful knockdown of CysLT1 by siRNA was confirmed by western blotting (Fig.5a). Silencing of CysLT1 expression consequently suppressed not only EGF-induced Tiam1 expression at both mRNA and protein levels, but also the second EGF-induced wave of Rac1 activation, lamellipodia formation and cell migration (Fig.5b,d,f–h). In contrast, silencing of CysLT1 had little effect on the first EGF-induced wave of Rac1 activation and the corresponding lamellipodia formation (Fig.5c,e). These results indicate that 5-LOX/LTC4(D4)/CysLT1 signaling regulated EGF-induced expression of Tiam1, resulting in the second EGF-induced wave of Rac1 activation and cell migration.
Affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.