Introduction of ID2 Enhances Invasiveness in ID2-null Oral Squamous Cell Carcinoma Cells via the SNAIL Axis

Cancer Genomics Proteomics. 2016;13(6):493-497. doi: 10.21873/cgp.20012.

Abstract

Aim: Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells.

Materials and methods: We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP).

Results: ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1).

Conclusion: ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2-SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC.

Keywords: Inhibitor of differentiation; SNAIL; epithelial–mesenchymal transition; invasion; matrix metalloproteinase.

MeSH terms

  • Cadherins / biosynthesis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Differentiation Protein 2 / biosynthesis
  • Inhibitor of Differentiation Protein 2 / genetics*
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / therapy
  • Neoplasm Invasiveness / genetics
  • Signal Transduction / genetics
  • Snail Family Transcription Factors / genetics*
  • Vimentin / biosynthesis

Substances

  • Cadherins
  • ID2 protein, human
  • Inhibitor of Differentiation Protein 2
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Vimentin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2