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5-Lipoxygenase and cysteinyl leukotriene receptor 1 regulate epidermal growth factor-induced cell migration through Tiam1 upregulation and Rac1 activation.

Magi S, Takemoto Y, Kobayashi H, Kasamatsu M, Akita T, Tanaka A, Takano K, Tashiro E, Igarashi Y, Imoto M - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.

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5-lipoxygenase (5-LOX) inhibitors and cysteinyl leukotriene receptor 1 (CysLT1) antagonists inhibit the second epidermal growth factor (EGF)-induced wave of Rac1 activation. The effect of 5-LOX inhibitors (a, b) and CysLT1 antagonists (c, d) on EGF-induced Rac1 activation. A431 cells were pretreated with the indicated concentrations of compounds for 15 min and stimulated with EGF. After 5 min (first wave; a, c) or 12 h (second wave; b, d), the cells were examined for active Rac1 by pull-down assay.
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fig03: 5-lipoxygenase (5-LOX) inhibitors and cysteinyl leukotriene receptor 1 (CysLT1) antagonists inhibit the second epidermal growth factor (EGF)-induced wave of Rac1 activation. The effect of 5-LOX inhibitors (a, b) and CysLT1 antagonists (c, d) on EGF-induced Rac1 activation. A431 cells were pretreated with the indicated concentrations of compounds for 15 min and stimulated with EGF. After 5 min (first wave; a, c) or 12 h (second wave; b, d), the cells were examined for active Rac1 by pull-down assay.

Mentions: Previously we reported that EGF induced distinct waves of Rac1 activation, and that the second wave Rac1 activation regulated the second wave of lamellipodia formation.6 Because 5-LOX inhibitors inhibited this second wave, we next examined the effect of 5-LOX inhibitors on the second wave of Rac1 activation. As shown in Figure3(a,b), both BU-4664L and AA-861 inhibited the second wave at a dose range similar to that that inhibited lamellipodia formation (Fig.3b). In contrast, both inhibitors failed to inhibit the first wave of Rac1 activation 2 min after EGF stimulation (Fig.3a). These results suggest that the second EGF-induced wave of Rac1 activation was mediated by LTC4 and LTD4 produced by 5-LOX in A431 cells.


5-Lipoxygenase and cysteinyl leukotriene receptor 1 regulate epidermal growth factor-induced cell migration through Tiam1 upregulation and Rac1 activation.

Magi S, Takemoto Y, Kobayashi H, Kasamatsu M, Akita T, Tanaka A, Takano K, Tashiro E, Igarashi Y, Imoto M - Cancer Sci. (2014)

5-lipoxygenase (5-LOX) inhibitors and cysteinyl leukotriene receptor 1 (CysLT1) antagonists inhibit the second epidermal growth factor (EGF)-induced wave of Rac1 activation. The effect of 5-LOX inhibitors (a, b) and CysLT1 antagonists (c, d) on EGF-induced Rac1 activation. A431 cells were pretreated with the indicated concentrations of compounds for 15 min and stimulated with EGF. After 5 min (first wave; a, c) or 12 h (second wave; b, d), the cells were examined for active Rac1 by pull-down assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317946&req=5

fig03: 5-lipoxygenase (5-LOX) inhibitors and cysteinyl leukotriene receptor 1 (CysLT1) antagonists inhibit the second epidermal growth factor (EGF)-induced wave of Rac1 activation. The effect of 5-LOX inhibitors (a, b) and CysLT1 antagonists (c, d) on EGF-induced Rac1 activation. A431 cells were pretreated with the indicated concentrations of compounds for 15 min and stimulated with EGF. After 5 min (first wave; a, c) or 12 h (second wave; b, d), the cells were examined for active Rac1 by pull-down assay.
Mentions: Previously we reported that EGF induced distinct waves of Rac1 activation, and that the second wave Rac1 activation regulated the second wave of lamellipodia formation.6 Because 5-LOX inhibitors inhibited this second wave, we next examined the effect of 5-LOX inhibitors on the second wave of Rac1 activation. As shown in Figure3(a,b), both BU-4664L and AA-861 inhibited the second wave at a dose range similar to that that inhibited lamellipodia formation (Fig.3b). In contrast, both inhibitors failed to inhibit the first wave of Rac1 activation 2 min after EGF stimulation (Fig.3a). These results suggest that the second EGF-induced wave of Rac1 activation was mediated by LTC4 and LTD4 produced by 5-LOX in A431 cells.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.

Show MeSH
Related in: MedlinePlus