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肌动蛋白结合蛋白 Espin:黑色素瘤的一种新型转移调节蛋白。

Actin-binding protein, Espin: a novel metastatic regulator for melanoma.

机构信息

Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.

出版信息

Mol Cancer Res. 2014 Mar;12(3):440-6. doi: 10.1158/1541-7786.MCR-13-0468-T. Epub 2013 Dec 13.

Abstract

UNLABELLED

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.

摘要

未标记

Espin 是一种多功能肌动蛋白结合蛋白,具有多种同工型,与内耳毛细胞的静纤毛和感觉细胞的微绒毛特化结构有特殊的联系。然而,目前尚无报道表明 Espin 在癌症(包括黑色素瘤)中表达和功能。本研究表明,在 RET 转基因小鼠(RET 小鼠)自发形成的黑色素瘤中,Espin 的表达显著增加。重要的是,Espin 耗尽的 Mel-ret 黑色素瘤细胞的侵袭能力明显低于对照黑色素瘤细胞,其片状伪足、粘着斑激酶(FAK)和 GTP-Rac1 活性降低。相应地,在体内黑色素瘤转移模型中,Espin 耗尽的 Mel-ret 黑色素瘤细胞的转移灶比例明显低于对照黑色素瘤细胞。此外,Espin 可能是人类黑色素瘤的一种新的生物标志物,因为我们的免疫组织化学分析数据显示,Espin 阳性细胞在人原发性和转移性黑色素瘤中的百分比明显高于黑色素痣细胞。总之,这些结果表明,Espin 不仅是黑色素瘤的转移调节剂,也是疾病进展的潜在生物标志物。

含义

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。

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