Gli promotes tumor progression through regulating epithelial-mesenchymal transition in non-small-cell lung cancer
Gli promotes tumor progression through regulating epithelial-mesenchymal transition in non-small-cell lung cancer
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Gli通过调节非小细胞肺癌上皮间质转化促进肿瘤进展
DOI：
10.1186/s13019-020-1049-x
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发表时间：
2020-01-13
影响因子：
1.6
通讯作者：
Wang, Lei
中科院分区：
文献类型：
--
作者：
Jiang, Long;Huang, Jia;Wang, Lei
简介：肺癌是全球癌症相关死亡的主要原因。非小细胞肺癌（non-small cell lung cancer，NSCLC）是肺癌的一种常见类型。NSCLC通常经历上皮-间质转化（EMT）。控制这一过程的组件，因此有前途的治疗targets.Materials和方法：Gli/EMT蛋白表达水平进行了检查，通过蛋白质印迹在配对的NSCLC患者组织和NSCLC细胞系。进行功能分析以研究NSCLC细胞系中的SHH/Gli信号传导和EMT。MTS细胞活力，荧光素酶报告，和蛋白质印迹法进行分析途径的活动，而伤口愈合和transwell试验进行测量细胞迁移和invasion.Results：较高的Gli 1表达检测肿瘤样本比配对正常组织。在肿瘤组织中观察到EMT生物标志物的差异表达和p-AKT的活化。N-Shh刺激细胞显著增加NSCLC细胞系中的报告子活性，而Gli-i处理转染细胞显示较少的相对报告子活性。当进行Gli-i和N-Shh处理时，NSCLC细胞系继续表现出降低的Gli转录活性。Gli抑制与p-AKT、N-钙粘蛋白和波形蛋白的表达水平降低相关。Gli 1和Gli 2的敲除均显示EMT、迁移和侵袭能力降低。N-Shh刺激的细胞表现出更大的流动性。此外，AKT-i处理的细胞也表现出抑制EMT activity.Conclusions：这项研究提供了证据的Gli信号通路的异常上调和Gli与AKT和EMT标志物在NSCLC中的表达之间的强关联。
Introduction: Lung cancer is the leading causes of cancer-related deaths globally. The most frequent histologic type of lung cancer is non-small-cell lung cancer (NSCLC). NSCLC often undergo epithelial-mesenchymal transition (EMT). The components that control this process are thus promising therapeutic targets.Materials and methods: Gli/EMT protein expression levels were examined by western blot in paired NSCLC patient tissues and NSCLC cell lines. Functional analyses were performed to investigate SHH/Gli signaling and EMT in NSCLC cell lines. MTS cell viability, luciferase reporter, and western blot assays were performed to analyze pathway activity, while wound healing and transwell assays were executed to measure cell migration and invasion.Results: Higher Gli1 expressions were detected in tumor samples than in paired normal tissues. Differential expression of EMT biomarkers and activation of p-AKT were observed in tumor tissues. N-Shh stimulation of cells significantly increased reporter activity in NSCLC cell lines, while Gli-i treatment of transfected cells showed less relative reporter activity. When subjected to both Gli-i and N-Shh treatment, NSCLC cell lines continued to demonstrate decreased Gli transcriptional activity. Gli inhibition is associated with decreased expression level of p-AKT, N-cadherin and Vimentin. Knockdown of both Gli1 and Gli2 showed decreased EMT, migrative and invasive ability. Cells stimulated by N-Shh demonstrated greater mobility. In addition, AKT-i treated cells also demonstrated inhibited EMT activity.Conclusions: This study provides evidence for aberrant upregulation of the Gli signaling pathway and a strong association between expression of Gli versus AKT and EMT markers in NSCLC.