Yang Fenglian, Gu Yanan, Zhao Zehang, Huang Jing, Jiang Wen G, Cheng Shan
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China.
Anticancer Res. 2017 Aug;37(8):4405-4414. doi: 10.21873/anticanres.11835.
BACKGROUND/AIM: Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) has been reported to interact with many cancer-related proteins and plays an important role in cancer progression. However, little is known about the biological functions of NHERF1 in lung cancer cells. The aim of the current study was to explore whether NHERF1 is involved in transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer cells.
The expression of NHERF1 and EMT-associated markers including E-cadherin, N-cadherin, snail family transcriptional repressor 1 (SNAI1) and snail family transcriptional repressor 2 (SLUG) were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The migratory properties of cells were assessed using a wound-healing assay.
TGF-β1-induced a pro-migratory response in the A549 lung cancer cell line, that was consistently associated with corresponding changes in the expression levels of EMT-related genes. The expression of NHERF1 significantly decreased in the TGF-β1-induced A549 cells. Overexpression of NHERF1 significantly inhibited the migratory ability of cells and reversed the TGF-β1-induced mesenchymal phenotype of A549 cells.
These data showed an important role of NHERF1 in the EMT of non-small-cell lung cancer cells, as well as migration.
背景/目的：据报道，钠氢交换调节因子1（NHERF1）可与多种癌症相关蛋白相互作用，并在癌症进展中发挥重要作用。然而，关于NHERF1在肺癌细胞中的生物学功能却知之甚少。本研究的目的是探讨NHERF1是否参与转化生长因子（TGF）-β1诱导的非小细胞肺癌细胞上皮-间质转化（EMT）。
通过逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法分析NHERF1以及与EMT相关的标志物（包括E-钙黏蛋白、N-钙黏蛋白、蜗牛家族转录抑制因子1（SNAI1）和蜗牛家族转录抑制因子2（SLUG））的表达。使用伤口愈合试验评估细胞的迁移特性。
TGF-β1在A549肺癌细胞系中诱导了促迁移反应，这与EMT相关基因表达水平的相应变化一致。在TGF-β1诱导的A549细胞中，NHERF1的表达显著降低。NHERF1的过表达显著抑制了细胞的迁移能力，并逆转了TGF-β1诱导的A549细胞的间质表型。
这些数据表明NHERF1在非小细胞肺癌细胞的EMT以及迁移过程中发挥重要作用。
