12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells

• Main Authors: Yang XH, Zhuang MK, Xie WH, Du F, Huang YH, Chen ZX, Chen FL, Wang XZ
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-07-01
• Series: OncoTargets and Therapy
• Subjects: 12-lipoxygenase; EMT; Wnt/β-catenin pathway; gastric cancer
• Online Access: https://www.dovepress.com/12-lipoxygenase-promotes-epithelial-mesenchymal-transition-via-the-wnt-peer-reviewed-article-OTT

Xiao-Huang Yang, Ming-Kai Zhuang, Wen-Hui Xie, Fan Du, Yue-Hong Huang, Zhi-Xin Chen, Feng-Lin Chen, Xiao-Zhong WangDepartment of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, People’s Republic of ChinaBackground: 12-Lipoxygenase (12-LOX) plays a major role in the progression and metastasis of various types of cancer. In gastric cancer (GC), the expression level of 12-LOX is significantly up-regulated; however, its function, and underlying mechanism of action remain unclear.Methods: The mRNA and protein expression levels of 12-LOX were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses, respectively, in GC cell lines. 12-LOX expression was stably up-regulated using lentiviral vector in BGC823 and MGC803 cells, and cell-counting kit-8 (CCK8), colony formation, and invasion assays were performed to verify the function of 12-LOX in proliferation and metastasis. In addition, the expression levels of epithelial-mesenchymal transition (EMT) differentiation markers and downstream targets of the Wnt/β-catenin signaling pathway were examined by Western blotting. A nude mouse model of tumor growth and metastasis was established to investigate the role of 12-LOX in vivo.Results: Our findings demonstrate that 12-LOX mRNA and protein were highly expressed in GC cell lines. 12-LOX overexpression promoted GC cell proliferation, migration, and invasion both in vitro and in vivo. In addition, up-regulation of 12-LOX promoted the EMT in GC cells, as reflected by a decrease in E-cadherin expression and an increase in N-cadherin and Snail expression. 12-LOX overexpression in GC cells also increased the expression of multiple downstream targets of the Wnt/β-catenin signaling pathway.Conclusion: These findings revealed that 12-LOX functions as an oncogene in promoting GC cell proliferation and metastasis in vitro and in vivo. In addition, 12-LOX might regulate the EMT via the Wnt/β-catenin signaling pathway, indicating a potential role for 12-LOX as a target in GC treatment.Keywords: 12-lipoxygenase, EMT, Wnt/β-catenin signaling pathway, gastric cancer