악성흑색종에서 Fascin과 MST2의 역할

Abstract

Background and Objectives: Fascin is an actin-bundling protein which is an essential element in cancer metastasis. Hippo pathway is a critical for carcinogenesis and cancer stem cell self-renewal. One of the core components of the Hippo pathway is mammalian ste20-like protein kinase (MST). The aim of this study was to investigate the roles and mechanisms of Fascin and MST2 on carcinogenesis in melanoma, which remains largely unknown. Materials and Methods: Surgically excised 30 cases of primary skin melanoma with adjacent non-tumorous skin tissue were conducted immunohistochemical staining for Fascin and MST2. The melanoma cell line WM793 was employed for the Fascin and MST2 knock-down and then analyzed by the Western blot assay, and the melanoma xenograft followed by Fascin knock-down in BALB/c mice and then analyzed by tumor size measuring and histopathologic assessment. Results: Immunohistochemical analysis showed increased expression of Fascin and decreased expression of MST2 in melanoma. Reverse correlation of Fascin and MST2 was statistically significant. Fascin siRNA oligonucleotides upregulated MST2 but MST2 siRNA oligonucleotides did not significantly change Fascin in the WM793 cell line. WM793 xenograft followed by Fascin knock-down inhibited tumor growth significantly in the animal study. Conclusions: Fascin is a regulator in the Hippo pathway through MST2 and plays an important role in melanoma carcinogenesis. Knock-down of Fascin reduces melanoma carcinogenesis, so Fascin could be a potential therapeutic target for melanoma.