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Updated: Mar 29, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Investigation of FOXM1 as a Potential New Target for Melanoma
Azusa Miyashita1, Satoshi Fukushima1, Satoshi Nakahara1
1Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Japan.
Abstract:
Recent studies have shown that immunotherapies and molecular targeted therapies are effective for advanced melanoma. Non-antigen-specific immunotherapies such as immunocheckpoint blockades have been shown to be effective in the treatment of advanced melanoma. However, the response rates remain low. To improve their efficacy, they should be combined with antigen-specific immunotherapy. Elevated expression of the transcription factor, Forkhead box M1 (FOXM1), has been reported in various human cancers, and it has been shown to have potential as a target for immunotherapy. The purpose of this study was to investigate the FOXM1 expression in human melanoma samples and cell lines, to evaluate the relationship between the FOXM1 expression and the clinical features of melanoma patients and to investigate the association between the FOXM1 and MAPK and PI3K/AKT pathways in melanoma cell lines. We conducted the quantitative reverse transcription PCR (qRT-PCR) and Western blotting analyses of melanoma cell lines, and investigated melanoma and nevus tissue samples by qRT-PCR and immunohistochemistry. We performed MEK siRNA and PI3K/AKT inhibitor studies and FOXM1 siRNA studies in melanoma cell lines. We found that FOXM1 was expressed in all of the melanoma cell lines, and was expressed in 49% of primary melanomas, 67% of metastatic melanomas and 10% of nevi by performing immunohistochemical staining. Metastatic melanoma samples exhibited significantly higher mRNA levels of FOXM1 (p = 0.004). Primary melanomas thicker than 2 mm were also more likely to express FOXM1. Patients whose primary melanoma expressed FOXM1 had a significantly poorer overall survival compared to patients without FOXM1 expression (p = 0.024). Downregulation of FOXM1 by siRNA significantly inhibited the proliferation of melanoma cells, and blockade of the MAPK and PI3K/AKT pathways decreased the FOXM1 expression in melanoma cell lines. In conclusion, FOXM1 is considered to be a new therapeutic target for melanoma.
Insights
Forkhead box M1 (FOXM1) is elevated in melanoma and linked to poorer survival. Inhibiting FOXM1 or targeting related pathways may offer new melanoma treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Advanced melanoma treatment benefits from immunotherapies and targeted therapies, but response rates are limited.
- Combining non-antigen-specific immunotherapies with antigen-specific approaches may improve efficacy.
- Forkhead box M1 (FOXM1) is a transcription factor overexpressed in cancers, showing potential as an immunotherapy target.
Purpose of the Study:
- Investigate FOXM1 expression in melanoma samples and cell lines.
- Correlate FOXM1 expression with clinical features in melanoma patients.
- Examine the association between FOXM1 and MAPK/PI3K/AKT pathways in melanoma.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) and Western blotting on melanoma cell lines.
- Immunohistochemistry on melanoma and nevus tissue samples.
- siRNA-mediated downregulation of FOXM1 and MEK, and PI3K/AKT pathway inhibition.
Main Results:
- FOXM1 expressed in all melanoma cell lines; 49% primary melanomas, 67% metastatic melanomas, 10% nevi.
- Metastatic melanomas showed significantly higher FOXM1 mRNA levels (p=0.004).
- Thicker primary melanomas (>2 mm) and poorer overall survival were associated with FOXM1 expression (p=0.024).
- FOXM1 downregulation inhibited melanoma cell proliferation; pathway blockade reduced FOXM1 expression.
Conclusions:
- FOXM1 is a potential therapeutic target for melanoma.
- FOXM1 expression correlates with melanoma progression and patient survival.
- Targeting FOXM1 and associated signaling pathways may enhance melanoma treatment.
