Skin melanoma cells produce diverse gelsolin (GSN) isoforms, which play non-redundant roles in cells' proliferation and motility

Ewa Mazurkiewicz-Stanek ¹, Aleksandra Makowiecka ², Iryna Kopernyk ²

⁰Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, Wrocław, Poland. ewa.mazurkiewicz@uwr.edu.pl.

Cancer Cell International +

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July 2, 2025

View abstract on PubMed

Summary

Gelsolin (GSN) isoforms play distinct roles in melanoma progression. A mixture of GSN isoforms is essential for melanoma cell survival and function, highlighting potential therapeutic targets.

Area Of Science

Molecular Biology
Cancer Research
Cell Biology

Background

Skin melanoma is a challenging cancer, especially when diagnosed late.
High gelsolin (GSN) levels correlate with advanced cutaneous melanoma.
The specific roles of diverse GSN isoforms in melanoma remain uninvestigated.

Purpose Of The Study

To determine if diverse GSN isoforms are produced by melanoma cells in vivo and in vitro.
To elucidate the specific functions of individual GSN isoforms in melanoma biology.

Main Methods

Immunocytochemical staining of melanoma tissue samples.
Bioinformatics analysis of GSN isoform transcript levels.
Functional assays using GSN knockout melanoma cells with restored single isoform production (migration, invasion, actin polymerization, proliferation).

Main Results

Human melanoma cells produce three GSN isoforms (secretory A, cytosolic B and C) in vitro and in vivo.
GSN-A enhances invasion; GSN-C promotes migration and filipodia formation.
GSN-B and GSN-C reduce filamentous actin; GSN-A and GSN-B decrease proliferation.

Conclusions

GSN isoforms are not redundant and exhibit distinct functions in melanoma.
A specific mixture of GSN isoforms is required for melanoma cell well-being.

Keywords:

Adhesion Cancer Gelsolin (GSN) Isoforms Motility Phenotypic heterogeneity Skin melanoma