12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells
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 r...
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doaj-333ecc3cf64548a0b2719c7f340500fd2020-11-24T21:17:10ZengDove Medical PressOncoTargets and Therapy1178-69302019-07-01Volume 12555155614705212-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cellsYang XHZhuang MKXie WHDu FHuang YHChen ZXChen FLWang XZXiao-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 cancerhttps://www.dovepress.com/12-lipoxygenase-promotes-epithelial-mesenchymal-transition-via-the-wnt-peer-reviewed-article-OTT12-lipoxygenaseEMTWnt/β-catenin pathwaygastric cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang XH Zhuang MK Xie WH Du F Huang YH Chen ZX Chen FL Wang XZ |
spellingShingle |
Yang XH Zhuang MK Xie WH Du F Huang YH Chen ZX Chen FL Wang XZ 12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells OncoTargets and Therapy 12-lipoxygenase EMT Wnt/β-catenin pathway gastric cancer |
author_facet |
Yang XH Zhuang MK Xie WH Du F Huang YH Chen ZX Chen FL Wang XZ |
author_sort |
Yang XH |
title |
12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells |
title_short |
12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells |
title_full |
12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells |
title_fullStr |
12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells |
title_full_unstemmed |
12-Lipoxygenase promotes epithelial–mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells |
title_sort |
12-lipoxygenase promotes epithelial–mesenchymal transition via the wnt/β-catenin signaling pathway in gastric cancer cells |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2019-07-01 |
description |
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 |
topic |
12-lipoxygenase EMT Wnt/β-catenin pathway gastric cancer |
url |
https://www.dovepress.com/12-lipoxygenase-promotes-epithelial-mesenchymal-transition-via-the-wnt-peer-reviewed-article-OTT |
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