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• W2005027400 abstract "Abstract Thymosin beta‐4 (Tβ4), actin‐sequestering protein, plays important roles in many cellular functions including cancer cell migrations. Glycogen synthase kinase (GSK) in Wnt signaling pathway is a key molecule to control intercellular interaction. Here, we investigated whether GSK‐3 activity is regulated by Tβ4 and it is associated with Tβ4‐mediated migration in gastric cancer cells. Various expression level of Tβ4 was observed in human gastric tumor tissues. Migration in gastric cancer cells, SNU638 and SNU668, was dependent on a relative expression level of Tβ4. Cell migration was higher in SNU668 with a higher expression level of Tβ4 than that in SNU638 with a lower Tβ4. Although the level of phosphorylated(p)‐GSK‐3α (inactive), β‐catenin, E‐cadherin and E‐cadherin:β‐catenin complex was relatively higher, p‐GSK‐3β (inactive) was lower in SNU638 compared to those in SNU668 cells. LiCl, GSK‐3α/β inhibitor, reduced lung metastasis of B16F10 mouse melanoma cells and SNU668 cell migration. Small interference (si)RNA of GSK‐3α increased SNU638 cell migration in accordance with the reduction of E‐cadherin:β‐catenin complex formation through a decrease in β‐catenin and E‐cadherin. Expression level of GSK‐3α/β, β‐catenin and E‐cadherin in SNU668 and SNU638 was reversed by Tβ4‐siRNA and by the treatment with acetylated‐serine‐aspartic acid‐lysine‐proline (SDKP) tetrapeptide of Tβ4, respectively. E‐cadherin expression in SNU638 cells was decreased by β‐catenin‐siRNA. PD98059, MEK inhibitor, or U0126, ERK inhibitor, reduced SNU668 cell migration accompanying an increase in p‐GSK‐3α, β‐catenin and E‐cadherin. Taken together, data indicated that the expression of GSK‐3α, β‐catenin and E‐cadherin could be negatively regulated by Tβ4‐induced ERK phosphorylation. It suggests that Tβ4 could be a novel regulator to control Wnt signaling pathways." @default.
• W2005027400 created "2016-06-24" @default.
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• W2005027400 date "2012-03-28" @default.
• W2005027400 modified "2023-10-18" @default.
• W2005027400 title "Regulation of glycogen synthase kinase-3 by thymosin beta-4 is associated with gastric cancer cell migration" @default.
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• W2005027400 doi "https://doi.org/10.1002/ijc.27490" @default.
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