C/EBPα Suppresses Lung Adenocarcinoma Cell Invasion and Migration by Inhibiting β-Catenin

Abstract

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. Methods: 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. Results: 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. Conclusion: 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.

CCAAT enhancer binding protein α suppresses proliferation, metastasis, and epithelial-mesenchymal transition of ovarian cancer cells via suppressing the Wnt/β-catenin signaling

“…In addition, CEBPA-mediated upregulation of PLIN2 promotes chronic myelocytic leukemia progression by -catenin signaling pathways [33]. In lung adenocarcinoma, CEBPA suppresses migration, invasion and EMT of lung adenocarcinoma cells by inhibiting the -catenin [20]. In our study, we found that knockout of CEBPA activated -catenin signaling in ovarian cancer cells, while CEBPA overexpression suppressed -catenin activation.…”

“…In breast cancer, CEBPA is required to maintaining epithelial homeostasis by repressing the expression of key mesenchymal markers and preventing EMT [17]. CEBPA is involved in the homeostasis of gastric epithelium [18], and represses migration and/or invasion of cervical squamous cell carcinoma and lung adenocarcinoma [19,20]. In our study, we found that CEBPA knockout facilitated migration, invasion and EMT of ovarian cancer cells, while overexpression of CEBPA exhibited opposite effects.…”

“…Indeed, CEBPA is crucial for epithelial maintenance by suppressing EMT of breast cancer cells [17]. In other studies, CEBPA is reported to associate with homeostasis of gastric epithelium [18], and suppress migration and/or invasion of cervical squamous cell carcinoma and lung adenocarcinoma [19,20]. As nearly 90% ovarian cancers are of epithelial origin, we speculated that CEBPA knockout might affect EMT of ovarian cancer cells.…”

Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway

“…It was shown that pioglitazone induced expression of a broad array of PPAR-γ target genes including C/EBPα in mice with paired box gene 8 fusion protein thyroid carcinomas [ 39 ]. Previous researches also reported that C/EBPα can inhibit lung cancer development through the p38α MAPK pathway and suppress lung cancer cell invasion and migration [ 40 , 41 ]. As the results showed, C/EBPα expression was increased and decreased to varying degrees by RGZ or LGZ when co-treatment with TGF-β1, maybe due to different mutational profiles of two thyroid cancer cell-lines [ 42 ].…”

Negative Effect of Reduced NME1 Expression on Recurrence-Free Survival in Early Stage Non-Small Cell Lung Cancer

“…Nuclear β-catenin forms a stable complex with members of the TCF/LEF transcription factor family and induces the expression of target genes such as c-MYC and CCND1 , and influences the metastatic cascade by regulating the expression of genes such as AXIN2 , SNAIL , ZEB1 , COX2 , and S100A4 [ 18 ]. It has been reported that the Wnt/β-catenin signaling pathway is involved in the invasion and metastasis of tumor cells in patients with NSCLC [ 19 , 20 , 21 , 22 ]. In addition to the nuclear translocation of β-catenin by NME1 silencing, Wnt/β-catenin-mediated resistance to cisplatin has been demonstrated in human cancers [ 23 , 24 ].…”