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Updated: Dec 20, 2025
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Paired Basic Amino Acid-cleaving Enzyme 4 (PCSK6): An Emerging New Target Molecule in Human Melanoma
Carsten Weishaupt1, Arianna Mastrofrancesco, Dieter Metze
1Department of Dermatology, University Hospital of Muenster, DE-48149 Münster, Germany.
Abstract:
Although recent therapeutic developments raise hope, melanoma remains a devastating disease with a need for new treatment targets. In other tumours prohormone convertases have been shown to be pro-tumourigenic as they are involved in processing preforms of matrix-metalloproteinases, growth factors and adhesion molecules. The aim of this study was to look for new treatment options for melanoma, by investigating the role of the prohormone convertase Paired basic Amino acid-Cleaving Enzyme 4 (PACE4/PCSK6) in melanoma cell lines and human melanoma tissue. PACE4-transfected A375 melanoma cells displayed significantly increased proliferation, MMP-2 production, gelatinase activity and migratory capacity in vitro compared with sham-transfected cells. In vivo, elevated PACE4 expression resulted in significantly increased tumour growth on immunodeficient mice. In the majority of 45 human primary melanomas and melanoma metastases ex vivo PACE4 immunoreactivity was detectable, while it was absent in in situ melanomas. These results indicate PACE4 as a regulator of melanoma cell aggressiveness.
Insights
Paired basic amino acid-cleaving enzyme 4 (PACE4) promotes melanoma cell aggressiveness. Elevated PACE4 expression increases proliferation, migration, and tumor growth, suggesting PACE4 as a potential therapeutic target for melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Melanoma necessitates novel therapeutic targets despite recent advancements.
- Prohormone convertases are implicated in tumor progression by processing key molecules like growth factors and matrix-metalloproteinases.
Purpose of the Study:
- To investigate the role of prohormone convertase Paired basic Amino acid-Cleaving Enzyme 4 (PACE4/PCSK6) in melanoma.
- To identify PACE4 as a potential therapeutic target for melanoma treatment.
Main Methods:
- PACE4 expression and function were assessed in A375 melanoma cell lines.
- In vitro assays measured proliferation, MMP-2 production, gelatinase activity, and migration.
- In vivo studies utilized immunodeficient mice to evaluate tumor growth.
- PACE4 immunoreactivity was examined in human primary melanomas and metastases.
Main Results:
- PACE4-transfected melanoma cells exhibited increased proliferation, MMP-2 production, gelatinase activity, and migration in vitro.
- Elevated PACE4 expression significantly enhanced tumor growth in vivo.
- PACE4 immunoreactivity was detected in most human melanoma tissues but not in situ melanomas.
Conclusions:
- PACE4 acts as a regulator of melanoma cell aggressiveness.
- PACE4 is a promising therapeutic target for melanoma treatment.
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