Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Department of Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Biochem Biophys Res Commun. 2023 Oct 8;676:182-189. doi: 10.1016/j.bbrc.2023.07.038. Epub 2023 Jul 24.
It has been reported that cadherin 6 (CDH6) upregulation is associated with enhanced epithelial-to-mesenchymal transition (EMT) in several types of solid tumor cells. The current study aimed to explore the effect of CDH6 on the migration and invasion of stomach adenocarcinoma (STAD) cells, the transcription factors involved in CDH6 dysregulation and their effect on mitochondrial fission. Bioinformatics analysis was performed using data extracted from the Genotype-Tissue Expression Project, the Cancer Genome Atlas and Kaplan-Meier plotter. AGS and HGC27 cells were used to establish an in vitro STAD cell model. The results showed that higher CDH6 expression was associated with significantly shorter overall survival in patients with STAD. In addition, CDH6 overexpression promoted wound healing, enhanced the invasion ability of tumor cells and increased mitochondrial fission. Glioma-associated oncogene family zinc finger 2 (GLI2) could bind to the CDH6 promoter and activate its transcription. Fluorescent labeling also showed that GLI2 overexpression promoted mitochondrial fission. However, CDH6 silencing significantly reduced mitochondrial fragmentation. Besides, GLI2 overexpression notably upregulated phosphorylated-focal adhesion kinase and dynamin-related protein 1. However, the above effects were largely abrogated by CDH6 knockdown. In conclusion, the present study suggested that the novel GLI2/CDH6 axis could enhance the migration, invasion and mitochondrial fission of STAD cells.
已有报道称，钙黏蛋白 6（CDH6）的上调与几种实体瘤细胞中增强的上皮-间充质转化（EMT）有关。本研究旨在探讨 CDH6 对胃腺癌（STAD）细胞迁移和侵袭的影响，以及涉及 CDH6 失调的转录因子及其对线粒体分裂的影响。使用从基因-组织表达项目、癌症基因组图谱和 Kaplan-Meier 绘图器中提取的数据进行了生物信息学分析。AGS 和 HGC27 细胞被用于建立体外 STAD 细胞模型。结果表明，STAD 患者中 CDH6 表达水平较高与总生存期明显缩短相关。此外，CDH6 过表达促进伤口愈合，增强肿瘤细胞的侵袭能力，并增加线粒体分裂。神经胶质瘤相关癌基因家族锌指蛋白 2（GLI2）可与 CDH6 启动子结合并激活其转录。荧光标记也表明 GLI2 过表达促进线粒体分裂。然而，CDH6 沉默显著减少了线粒体碎片化。此外，GLI2 过表达显著上调了磷酸化粘着斑激酶和动力相关蛋白 1。然而，CDH6 敲低显著削弱了上述作用。总之，本研究表明，新的 GLI2/CDH6 轴可增强 STAD 细胞的迁移、侵袭和线粒体分裂。
