5‐Lipoxygenase promotes epithelial–mesenchymal transition through the ERK signaling pathway in gastric cancer

作者：Hao Lin, Junyong Weng, Haitao Mei, Mingkai Zhuang, Xinzhu Xiao, Fan Du, Li‐Ying Lin, Ju‐Hua Wu, Zhixin Chen, Yuehong Huang, Fenglin Chen, Xiaozhong Wang · 发表于：Journal of Gastroenterology and Hepatology · 年份：2020 · DOI：10.1111/jgh.15184 · 被引用次数：21 · 研究领域：Cancer Cells and Metastasis、Cancer-related molecular mechanisms research、Cancer, Stress, Anesthesia, and Immune Response

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-β, 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 tu...