Abstract
Espin is a multifunctional actin-bundling protein with multiple isoforms, and has special connections to hair cell stereocilia and microvillar specializations of sensory cells in the inner ear. However, there have been no reports showing the expression and function of Espin in cancers, including melanoma. Here, it is demonstrated that Espin expression is significantly increased in melanomas that spontaneously developed in RET-transgenic mice (RET-mice). Importantly, the invasion capacity of Espin-depleted Mel-ret melanoma cells derived from a tumor of the RET-mouse was dramatically less than that of control melanoma cells with reductions of lamellipodia, focal adhesion kinase (FAK), and GTP-Rac1 activities. Correspondingly, the ratio of metastatic foci in Espin-depleted Mel-ret melanoma cells was significantly less than that of control melanoma cells in an in vivo melanoma metastasis model. Moreover, Espin could be a novel biomarker of melanoma in humans, because our immunohistochemical analysis data reveal that percentages of Espin-positive cells in human primary and metastatic melanomas were significantly higher than that of cells in melanocytic nevi. Together, these results indicate that Espin is not only a metastatic regulator for melanoma but also a potential biomarker of disease progression. Actin-binding protein Espin is expressed in melanoma, affects metastasis, and is a potential target for melanoma therapy.
Highlights
The incidence of melanoma has increased by 3.1% every year and its incidence rate has doubled over a 10-year period [1]
We first showed that Espin transcript expression levels in melanomas were more than 200-fold higher than those in benign melanocytic tumors in RET-mice by quantitative real-time PCR analysis using primers, which recognize all isoforms of the Espin transcript (Supplementary Fig. S2A)
Because our previous study showed that melanomas developed from benign melanocytic tumors in RET-mice [9], the results suggest that increased Espin expression level in melanoma is associated with malignant transformation
Summary
The incidence of melanoma has increased by 3.1% every year and its incidence rate has doubled over a 10-year period [1]. Melanoma is the most serious skin cancer and is highly invasive and resistant to conventional therapy [2]. Identification of a molecule associated with melanoma growth, progression, and metastasis will provide new insights into the design of a biomarker and a novel therapeutic strategy for melanoma. Preventing or eliminating metastasis is one of the most important challenges for therapeutic intervention. Several regulatory molecules for cancer invasion and metastasis have recently been reported as candidates for clinical applications [3]. An effective therapy for melanoma has not yet been established [2]
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