Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail
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Updated: Oct 8, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
I Poser1, D Domínguez, A G de Herreros
1Institute of Pathology, Medical School Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, D-52074 Aachen, Germany.
Abstract:
Malignant transformation of melanocytes frequently coincides with loss of E-cadherin expression. Here we show that loss of E-cadherin in melanoma cell lines does not involve mutations in the E-cadherin gene, promoter methylation, or alterations in expression of AP-2 transcription factors as suggested previously. In a panel of different melanoma cell lines, E-cadherin expression was negatively regulated by up-regulation of the transcription factor Snail. In comparison with primary human melanocytes, where Snail expression was not detected by reverse transcription-polymerase chain reaction, significant expression was found in all eight melanoma cell lines. In parallel, Western blot and reverse transcription-polymerase chain reaction analysis revealed strong reduction of E-cadherin expression in the melanoma cells. Consistently, transient transfection of a Snail expression plasmid into human primary melanocytes led to significant down-regulation of E-cadherin, whereas transient and stable transfection of an antisense Snail construct induced reexpression of E-cadherin in Mel Ju and Mel Im melanomas. In summary, we conclude that activation of Snail expression plays an important role in down-regulation of E-cadherin and tumorigenesis of malignant melanomas.
Insights
Loss of E-cadherin in melanoma is not due to gene mutations but is linked to increased Snail transcription factor. This finding is crucial for understanding melanoma tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Malignant transformation of melanocytes often involves E-cadherin downregulation.
- Previous hypotheses suggested gene mutations, promoter methylation, or AP-2 alterations as causes.
Purpose of the Study:
- To investigate the regulatory mechanisms behind E-cadherin loss in melanoma.
- To determine the role of the transcription factor Snail in E-cadherin expression in melanoma cells.
Main Methods:
- Analysis of E-cadherin and Snail expression in melanoma cell lines and primary melanocytes.
- Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.
- Transient and stable transfection experiments using Snail expression and antisense constructs.
Main Results:
- E-cadherin loss in melanoma cell lines was not attributed to E-cadherin gene mutations, promoter methylation, or AP-2 factor alterations.
- Snail transcription factor expression was significantly upregulated in all tested melanoma cell lines compared to primary melanocytes.
- Increased Snail expression correlated with reduced E-cadherin levels; Snail downregulation restored E-cadherin expression.
Conclusions:
- Activation of Snail expression is a key mechanism driving E-cadherin downregulation in malignant melanomas.
- Snail plays a significant role in the tumorigenesis of malignant melanomas.
- Targeting Snail may offer a therapeutic strategy for melanoma treatment.
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