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Fascin 调控 Hippo 通路,对黑色素瘤的发生很重要。

Fascin Regulates the Hippo Pathway and Is Important for Melanoma Development.

机构信息

Department of Pathology, College of Medicine, Chosun University, Gwangju, Republic of Korea.

Department of Pathology, College of Medicine, Chosun University, Gwangju, Republic of Korea

出版信息

Anticancer Res. 2021 May;41(5):2403-2410. doi: 10.21873/anticanres.15015.

Abstract

BACKGROUND/AIM: Fascin, an actin-bundling protein, plays an essential role in cancer metastasis. The Hippo pathway is critical for carcinogenesis and cancer stem cell self-renewal. Mammalian STE20-like kinase (MST) is a core component of the Hippo pathway. However, whether fascin and MST2 affect melanoma remain largely unknown. This study aimed to investigate the role of fascin and MST2 in melanoma development.

MATERIALS AND METHODS

Surgically excised skin melanomas and the adjacent non-tumorous skin tissue from 30 cases were analyzed using immunohistochemistry for fascin and MST2. The melanoma cell line WM793 was employed for fascin and MST2 knock-down followed by western blotting, and melanoma xenografting in BALB/c mice.

RESULTS

Immunohistochemistry revealed increased expression of fascin and decreased expression of MST2 in melanoma. The reverse correlation of fascin and MST2 was statistically significant. Fascin siRNA upregulated MST2 expression; however, MST2 siRNA did not significantly affect fascin expression in the WM793. WM793 xenografting followed by fascin knock-down inhibited tumor growth significantly in the animal study.

CONCLUSION

Fascin is a regulator of the Hippo pathway and plays an important role in melanoma development. Therefore, fascin could be a potential therapeutic target for melanoma.

摘要

背景/目的:Fascin 是一种肌动蛋白成束蛋白,在癌症转移中发挥着重要作用。Hippo 通路对于癌症发生和癌症干细胞自我更新至关重要。哺乳动物 STE20 样激酶(MST)是 Hippo 通路的核心组成部分。然而,Fascin 和 MST2 是否影响黑色素瘤在很大程度上尚不清楚。本研究旨在探讨 Fascin 和 MST2 在黑色素瘤发展中的作用。

材料和方法

采用免疫组织化学法分析 30 例手术切除的皮肤黑色素瘤及其相邻非肿瘤皮肤组织中的 Fascin 和 MST2。采用 Fascin 和 MST2 敲低的 WM793 黑色素瘤细胞系进行 Western blot 分析,并在 BALB/c 小鼠中进行黑色素瘤异种移植。

结果

免疫组织化学显示黑色素瘤中 Fascin 表达增加,MST2 表达降低。Fascin 和 MST2 的负相关具有统计学意义。Fascin siRNA 上调 MST2 表达;然而,MST2 siRNA 对 WM793 中的 Fascin 表达没有显著影响。WM793 异种移植后 Fascin 敲低显著抑制了动物研究中的肿瘤生长。

结论

Fascin 是 Hippo 通路的调节剂,在黑色素瘤的发展中起着重要作用。因此,Fascin 可能是黑色素瘤的一个潜在治疗靶点。

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