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

Cell Physiol Biochem. 2017;42(5):1779-1788. doi: 10.1159/000479457. Epub 2017 Jul 26.

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.

Keywords: C/EBPα; Invasion; Lung adenocarcinoma; Migration; β-catenin.

MeSH terms

  • A549 Cells
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Epithelial-Mesenchymal Transition
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Real-Time Polymerase Chain Reaction
  • Transcription, Genetic
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • beta Catenin