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Updated: Aug 7, 2025

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but
Olga Bugaeva1, Pilvi Maliniemi2, Wenche S Prestvik3
11Department of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, University of Helsinki, Helsinki, Finland. olga.i.bugaeva@gmail.com.
Abstract:
Melanoma is a highly metastatic tumour originating from neural crest-derived melanocytes. The aim of this study was to analyse the expression of neuron navigator 3 (NAV3) in relation to membrane type-1 matrix metalloproteinase MMP14, a major regulator of invasion, in 40 primary melanomas, 15 benign naevi and 2 melanoma cell lines. NAV3 copy number changes were found in 18/27 (67%) primary melanomas, so that deletions dominated (16/27 of samples, 59%). NAV3 protein was found to be localized at the leading edge of migrating melanoma cells in vitro. Silencing of NAV3 reduced both melanoma cell migration in 2-dimensional conditions, as well as sprouting in 3-dimensional collagen I. NAV3 protein expression correlated with MMP14 in 26/37 (70%) primary melanomas. NAV3 and MMP14 were co-expressed in all tumours with Breslow thickness < 1 mm, in 11/23 of mid-thickness tumours (1-5 mm), but in only 1/6 samples of thick (> 5 mm) melanomas. Altogether, NAV3 number changes are frequent in melanomas, and NAV3 and MMP14, while expressed in all thin melanomas, are often downregulated in thicker tumours, suggesting that the lack of both NAV3 and MMP14 favours melanoma progression.
Insights
Neuron navigator 3 (NAV3) and MMP14 are frequently altered in melanoma. Their downregulation in thicker melanomas suggests they may inhibit melanoma progression and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Melanoma is a skin cancer originating from melanocytes.
- Metastasis is a hallmark of aggressive melanoma.
- MMP14 is a key regulator of cancer cell invasion.
Purpose of the Study:
- To analyze the expression of NAV3 in relation to MMP14 in primary melanomas.
- To investigate the role of NAV3 in melanoma cell migration and invasion.
- To correlate NAV3 and MMP14 expression with melanoma thickness.
Main Methods:
- Analysis of NAV3 copy number changes and protein expression in melanoma samples.
- In vitro studies using melanoma cell lines to assess the effect of NAV3 silencing on migration and invasion.
- Correlation analysis between NAV3 and MMP14 expression and clinicopathological features, including Breslow thickness.
Main Results:
- NAV3 copy number alterations (mainly deletions) were frequent in primary melanomas (67%).
- NAV3 protein localized to the leading edge of migrating melanoma cells and its silencing reduced cell migration and invasion.
- NAV3 and MMP14 expression correlated and were co-expressed in thin melanomas (<1 mm), but often downregulated in thicker tumors (>5 mm).
Conclusions:
- NAV3 copy number changes are common in melanoma.
- NAV3 plays a role in melanoma cell migration and invasion.
- Downregulation of both NAV3 and MMP14 in thicker melanomas suggests their involvement in inhibiting melanoma progression.
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