Lu Jinchang, Du Chunling, Yao Junxia, Wu Bo, Duan Yanhong, Zhou Lei, Xu Donghui, Zhou Feng, Gu Liang, Zhou Hong, Sun Yingxin
Department of Respiratory Medicine, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Pathology, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
Cell Physiol Biochem. 2017;42(5):1779-1788. doi: 10.1159/000479457. Epub 2017 Jul 26.
BACKGROUND/AIMS: The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPα expression in many cancers suggests a possible role for C/EBPα as a tumor suppressor, the functions of C/EBPα in lung adenocarcinoma remain unclear.
Here, C/EBPα expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPα on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms.
C/EBPα was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPα significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPα overexpression suppressed the epithelial-mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPα suppressed the transcription of β-catenin and downregulated the levels of its downstream targets.
Our data suggest that C/EBPα inhibits lung adenocarcinoma cell invasion and migration by suppressing β-catenin-mediated EMT in vitro. Thus, C/EBPα may be helpful as a potential target for treatment of lung adenocarcinoma.
背景/目的:转录因子CCAAT/增强子结合蛋白α(C/EBPα)是一种碱性亮氨酸拉链转录因子,在肿瘤进展中起重要作用。尽管在许多癌症中C/EBPα表达降低或缺失提示其可能作为肿瘤抑制因子发挥作用,但C/EBPα在肺腺癌中的功能仍不清楚。
本研究通过qRT-PCR和免疫组化检测了26例肺腺癌及癌旁组织样本中C/EBPα的表达水平。进行细胞Transwell实验、伤口愈合实验和三维球体侵袭实验以评估C/EBPα对肺腺癌细胞体外迁移和侵袭的影响。采用蛋白质免疫印迹法分析潜在机制。
发现肺腺癌组织中C/EBPα表达低于癌旁组织。C/EBPα过表达显著抑制肺腺癌细胞的迁移和侵袭。此外,C/EBPα过表达抑制了上皮-间质转化(EMT),其特征为上皮标志物增加和间质标志物减少。进一步研究表明,C/EBPα抑制β-连环蛋白的转录并下调其下游靶点的水平。
我们的数据表明,C/EBPα在体外通过抑制β-连环蛋白介导的EMT来抑制肺腺癌细胞的侵袭和迁移。因此,C/EBPα可能作为肺腺癌治疗的潜在靶点。