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Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland
Tomoki Sumida1, Akiko Ishikawa2, Hiroyuki Nakano1
1Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 8128582, Japan.
Abstract:
Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression.
Insights
Inhibitors of DNA-binding protein 2 (ID2) promote aggressive salivary gland cancer (SGC) phenotypes. Reducing ID2 expression in SGC cells decreases aggressiveness and offers a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Inhibitors of DNA-binding (ID) proteins regulate basic helix-loop-helix transcription factors, influencing cell proliferation and differentiation.
- Previous research identified high ID1 expression in aggressive salivary gland cancer (SGC) cells.
- This study investigates the role of ID2 in SGC progression.
Purpose of the Study:
- To determine the expression and function of ID2 in aggressive SGC cells.
- To evaluate the therapeutic potential of targeting ID2 in SGC.
Main Methods:
- Investigated ID2 expression in SGC cells.
- Performed ID2 knockdown experiments.
- Assessed changes in cell behavior, including differentiation markers (N-cadherin, vimentin, Snail, E-cadherin), cell shape, invasion, and matrix metalloproteinase 9 (MMP-9) expression.
Main Results:
- ID2 is expressed in aggressive SGC cells.
- ID2 knockdown significantly reduced N-cadherin, vimentin, and Snail expression.
- ID2 knockdown induced E-cadherin expression, leading to a more differentiated phenotype and altered cell shape.
- Knockdown of ID2 suppressed cell invasion and MMP-9 expression.
Conclusions:
- ID2 expression is crucial for maintaining the aggressive phenotype of SGC cells.
- Repression of ID2 leads to reduced SGC cell aggressiveness.
- ID2 represents a promising therapeutic target for SGC progression.
