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

Abstract

Background 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.

Establishment of a Novel In Vitro Model of Endometriosis with Oncogenic KRAS and PIK3CA Mutations for Understanding the Underlying Biology and Molecular Pathogenesis

“…A previous study reported that LOX cooperates with SNAIL at the protein level to facilitate the EMT and, thus, increases the invasive ability of breast cancer cell lines [46]. Another study also claimed that the overexpression of LOX promotes the proliferation, migration, and invasion of gastric cancer cell lines as well as high grade serous ovarian carcinoma [47,48]. In addition, PTX3 has pleiotropic roles in different types of cancer, such as gastric cancer, breast cancer, glioma, and prostate cancer.…”

Lidocaine alleviates cisplatin resistance and inhibits migration of MGC-803/DDP cells through decreasing miR-10b

“…Furthermore, a research also explained that the stimulation of mTOR was induced by the activation of AKT [33]. In addition to this, excessive researches showed that the β-catenin signaling pathway controlled the development and metastasis of gastric cancer cells [34]. A report also explicated that some miRNAs participated in cell proliferation and migration via regulating AKT/mTOR and βcatenin pathways in gastric cancer cells.…”

ML355 Modulates Platelet Activation and Prevents ABT-737 Induced Apoptosis in Platelets

“…The overexpression of ALOX12 gene, which codes for the arachidonate 12-lipoxygenase, is often a feature of cancer cells (Tomita et al, 2019). ALOX12 overexpression was shown to promote cancer metastasis (Zhong et al, 2018;Mi et al, 2020), epithelial-mesenchymal transition (Zhong et al, 2018;Yang et al, 2019), tumor growth, and cancer cell proliferation (Guo et al, 2011a). Conversely, the inhibition of 12-LOX decreases cancer cell proliferation and induces apoptosis of different cancer cell lines (Wong et al, 2001;Xu et al, 2012).…”