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.