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Lin, Hao; Weng, Junyong; Mei, Haitao; Zhuang, Mingkai; Xiao, Xinzhu; Du, Fan; Lin, Liying; Wu, Juhua; Chen, Zhixin; Huang, Yuehong; Chen, Fenglin and Wang, Xiaozhong (2020): 5-Lipoxygenase promotes epithelial-mesenchymal transition through the ERK signaling pathway in gastric cancer. In: Journal of Gastroenterology and Hepatology, Vol. 36, No. 2: pp. 455-466

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Background and Aim: 5-Lipoxygenase has been reported to enhance cell proliferation, migration, and invasion. Epithelial-mesenchymal transition is considered an important process for tumor metastasis and invasion. Methods The 5-lipoxygenase expression levels and the prognoses in patients with gastric cancer were evaluated by immunohistochemistry and by the log-rank test on Kaplan-Meier curves. We established 5-lipoxygenase-overexpressed and 5-lipoxygenase-silenced gastric cancer cells and measured migration, invasion, and epithelial-mesenchymal transition makers to examine the role of 5-lipoxygenase in gastric cancer in vitro. In vivo, 5-lipoxygenase-overexpressed gastric cancer cells were administered into mice by subcutaneous injection, intraperitoneal injection or splenic intravenous injection to study the proliferation or metastasis of 5-lipoxygenase in mice. Using the extracellular signal-regulated kinase pathway inhibitor U0126 and activator tumor growth factor-beta, we investigated the mechanism of epithelial-mesenchymal transition induced by 5-lipoxygenase in gastric cancer cells. Results 5-Lipoxygenase was upregulated in gastric cancer tissues and was related to poor overall survival in gastric cancer patients. 5-Lipoxygenase promoted gastric cancer cell proliferation, migration, and invasion and induced the process of epithelial-mesenchymal transition in gastric cancer cells. In the nude mouse model, mice with gastric cancer tumors overexpressing 5-LOX had a faster tumor growth rate and more severe abdominal and liver metastases than the control group. Inhibition of extracellular signal-regulated kinase signaling by U0126 or activation by tumor growth factor-beta neutralized the effect of 5-LOX overexpression or silencing on epithelial-mesenchymal transition. Conclusion 5-Lipoxygenase promotes epithelial-mesenchymal transition in gastric cancer by activating the extracellular signal-regulated kinase signaling pathway.

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