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埃兹蛋白通过调节 AKT 信号促进乳腺癌进展。

Ezrin promotes breast cancer progression by modulating AKT signals.

机构信息

Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China.

Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.

出版信息

Br J Cancer. 2019 Apr;120(7):703-713. doi: 10.1038/s41416-019-0383-z. Epub 2019 Feb 26.

Abstract

BACKGROUND

Ezrin, which is known as a cytoskeleton linker protein, is closely linked with the metastatic progression of cancer and is frequently abnormally expressed in aggressive cancer types. However, the possible involvement of Ezrin in metastasis and angiogenesis in breast cancer remains unclear.

METHODS

Immunohistochemical analysis of Ezrin was performed on both BC samples (n = 117) and normal epithelium samples (n = 47). In vivo and in vitro assays were performed to validate the effect of Ezrin on AKT pathway-mediated BC progression.

RESULTS

In this study, Ezrin was found to be upregulated in BC tissues, which was linked with aggressive tumour characteristics and poor prognosis. Moreover, we showed that Ezrin promotes BC proliferation, migration, invasion, and angiogenesis in vitro and in vivo. Mechanistic analysis showed that Ezrin interacted with AKT, and promoted its kinase activity, thereby regulating the AKT pathway in BC.

CONCLUSIONS

In all, we propose a model for an Ezrin/AKT oncoprotein axis, which provides novel insight into how Ezrin contributes to BC progression.

摘要

背景

Ezrin 作为一种细胞骨架连接蛋白,与癌症的转移进展密切相关,并且在侵袭性癌症类型中经常异常表达。然而,Ezrin 是否参与乳腺癌的转移和血管生成仍不清楚。

方法

对 BC 样本(n=117)和正常上皮样本(n=47)进行 Ezrin 的免疫组织化学分析。进行体内和体外实验,以验证 Ezrin 对 AKT 通路介导的 BC 进展的影响。

结果

在这项研究中,我们发现 Ezrin 在 BC 组织中上调,与侵袭性肿瘤特征和不良预后相关。此外,我们表明 Ezrin 在体外和体内促进 BC 的增殖、迁移、侵袭和血管生成。机制分析表明,Ezrin 与 AKT 相互作用,并促进其激酶活性,从而调节 BC 中的 AKT 通路。

结论

总之,我们提出了一个 Ezrin/AKT 癌蛋白轴的模型,为 Ezrin 如何促进 BC 进展提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d48/6461860/ff63aae96789/41416_2019_383_Fig1_HTML.jpg

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