Actin-Binding Protein, Espin: A Novel Metastatic Regulator for Melanoma
Actin-Binding Protein, Espin: A Novel Metastatic Regulator for Melanoma
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DOI：
10.1158/1541-7786.mcr-13-0468-t
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发表时间：
2013-12
影响因子：
5.2
通讯作者：
T. Yanagishita;I. Yajima;M. Kumasaka;Y. Kawamoto;T. Tsuzuki;Y. Matsumoto;D. Watanabe;Masashi Kato
中科院分区：
文献类型：
--
作者：
T. Yanagishita;I. Yajima;M. Kumasaka;Y. Kawamoto;T. Tsuzuki;Y. Matsumoto;D. Watanabe;Masashi Kato
ESpin是一种具有多种异构体的多功能肌动蛋白捆绑蛋白，与内耳感觉细胞的毛细胞立体纤毛和微绒毛特化有特殊的联系。然而，目前还没有关于ESpin在包括黑色素瘤在内的癌症中的表达和功能的报道。在这里，研究表明，在RET转基因小鼠(RET小鼠)自发发展的黑色素瘤中，ESpin的表达显著增加。重要的是，来自RET-小鼠肿瘤的ESpin耗竭的Mel-ret黑色素瘤细胞的侵袭能力显著低于对照黑色素瘤细胞，并降低了片状脂蛋白、粘着斑激酶(FAK)和GTP-rac1的活性。相应地，在体内黑色素瘤转移模型中，ESpin耗竭的Mel-ret黑色素瘤细胞的转移灶比例显著低于对照黑色素瘤细胞。此外，ESPIN可能是人类黑色素瘤的一个新的生物标志物，因为我们的免疫组织化学分析数据显示，在人类原发和转移性黑色素瘤中，ESPIN阳性细胞的百分比显著高于黑素细胞痣中的细胞。综上所述，这些结果表明ESpin不仅是黑色素瘤的转移调节因子，而且是疾病进展的潜在生物标记物。肌动蛋白结合蛋白ESpin在黑色素瘤中表达，影响转移，是黑色素瘤治疗的潜在靶点。摩尔癌症资源；12(3)；440-6。
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. Implications: Actin-binding protein Espin is expressed in melanoma, affects metastasis, and is a potential target for melanoma therapy. Mol Cancer Res; 12(3); 440–6. ©2013 AACR.