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Published on: January 5, 2017
Introduction of ID2 Enhances Invasiveness in ID2-null Oral Squamous Cell Carcinoma Cells via the SNAIL Axis
Y U Kamata1, Tomoki Sumida2, Yosuke Kobayashi1
1Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
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.
Insights
Inhibitor of DNA-binding 2 (ID2) expression promotes oral squamous cell carcinoma (OSCC) malignancy and invasion. Targeting the ID2-SNAIL pathway could offer new therapeutic strategies for OSCC treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Inhibitor of DNA-binding (ID) proteins are negative regulators of transcription factors involved in cell proliferation and differentiation.
- The specific role of ID2 in cancer progression, particularly in oral squamous cell carcinoma (OSCC), is not fully understood.
Purpose of the Study:
- To investigate the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells.
- To elucidate the mechanisms by which ID2 influences OSCC malignant phenotypes.
Main Methods:
- ID2 cDNA was introduced into ID2-null OSCC cells.
- Comparison of ID2-expressing cells versus empty-vector-transfected cells.
- Assessment of cell proliferation, invasion, and matrix metalloproteinase (MMP) expression and activity.
Main Results:
- ID2 expression enhanced malignant phenotypes in OSCC cells.
- Increased expression of N-cadherin, vimentin, and E-cadherin, indicating epithelial-mesenchymal transition (EMT).
- Significant increase in cell invasion and matrix metalloproteinase 2 (MMP2) expression and activity.
- Direct interaction identified between ID2 and SNAIL1 (snail family transcriptional repressor 1).
Conclusions:
- ID2 expression promotes a malignant phenotype, particularly invasive properties, in OSCC.
- The ID2-SNAIL axis is a key mediator of ID2-induced OSCC malignancy.
- ID2 emerges as a potential therapeutic target for oral squamous cell carcinoma.
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