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Updated: Jun 13, 2025

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Expression of LOXL3, NES, and SNAI1 in Melanoma Genesis and Progression
Zdenka Šitum Čeprnja1, Nela Kelam2, Marin Ogorevc2
1Department of Dermatovenerology, University Hospital of Split, 21000 Split, Croatia.
Abstract:
Melanoma is the most severe type of skin cancer and among the most malignant neoplasms in humans. With the growing incidence of melanoma, increased numbers of therapeutic options, and the potential to target specific proteins, understanding the basic mechanisms underlying the disease's progression and resistance to treatment has never been more important. LOXL3, SNAI1, and NES are key factors in melanoma genesis, regulating tumor growth, metastasis, and cellular differentiation. In our study, we explored the potential role of LOXL3, SNAI1, and NES in melanoma progression and metastasis among patients with dysplastic nevi, melanoma in situ, and BRAF+ and BRAF- metastatic melanoma, using immunofluorescence and qPCR analysis. Our results reveal a significant increase in LOXL3 expression and the highest NES expression in BRAF+ melanoma compared to BRAF-, dysplastic nevi, and melanoma in situ. As for SNAI1, the highest expression was observed in the metastatic melanoma group, without significant differences among groups. We found co-expression of LOXL3 and SNAI1 in the perinuclear area of all investigated subgroups and NES and SNAI1 co-expression in melanoma cells. These findings suggest a codependence or collaboration between these markers in melanoma EMT, suggesting new potential therapeutic interventions to block the EMT cascade that could significantly affect survival in many melanoma patients.
Insights
Researchers investigated lysyl oxidase like 3 (LOXL3), snail family transcriptional repressor 1 (SNAI1), and nestin (NES) in melanoma progression. Findings suggest these proteins collaborate in melanoma cell epithelial-mesenchymal transition, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Melanoma is a severe skin cancer with increasing incidence.
- Understanding melanoma progression and treatment resistance is crucial.
- LOXL3, SNAI1, and NES are implicated in melanoma growth and metastasis.
Purpose of the Study:
- To investigate the role of LOXL3, SNAI1, and NES in melanoma progression and metastasis.
- To analyze protein expression across different melanoma stages, including dysplastic nevi, melanoma in situ, and BRAF-positive/negative metastatic melanoma.
- To explore potential co-dependencies between these markers in melanoma.
Main Methods:
- Immunofluorescence analysis
- Quantitative Polymerase Chain Reaction (qPCR)
- Comparative analysis of protein expression in various melanoma subtypes.
Main Results:
- LOXL3 expression significantly increased in BRAF-positive melanoma.
- NES expression was highest in BRAF-positive melanoma.
- SNAI1 expression was highest in metastatic melanoma, with no significant inter-group differences.
- Co-expression of LOXL3/SNAI1 and NES/SNAI1 was observed, suggesting collaboration.
Conclusions:
- LOXL3, SNAI1, and NES play roles in melanoma progression and metastasis.
- Co-expression suggests a collaborative role in epithelial-mesenchymal transition (EMT).
- Targeting the EMT cascade involving these markers could offer new therapeutic strategies for melanoma.
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