Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition.
Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition.
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Ezrin 通过诱导上皮间质转化促进宫颈癌进展
DOI：
10.18632/oncotarget.7779
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发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Lin Z
中科院分区：
文献类型：
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作者：
Kong J;Di C;Piao J;Sun J;Han L;Chen L;Yan G;Lin Z
子宫颈癌是世界上第三大最常见的女性癌症。晚期子宫颈癌的治疗选择有限，导致高死亡率。Ezrin是一种膜-细胞骨架结合蛋白，最近被报道作为肿瘤启动子，我们之前指出Ezrin的异常定位和过表达可能是宫颈癌预后评估的独立有效的生物标志物。在这项研究中，我们发现Ezrin是宫颈癌上皮-间质转化（EMT）和转移的调节因子。Ezrin敲除抑制体外和体内宫颈癌细胞系的非锚定生长、细胞迁移和侵袭。在ezrin缺失的细胞中，EMT被抑制，E-cadherin和Cytokeratin-18 （CK-18）上调，间充质标志物下调。Ezrin敲除也诱导Akt磷酸化。这些结果提示Ezrin在宫颈癌中作为EMT调节因子和肿瘤启动子，并且Ezrin的下调可能通过磷酸肌肽3-激酶/Akt通路抑制宫颈癌的进展。免疫组化结果显示Ezrin蛋白表达模式与宫颈癌淋巴血管浸润状况密切相关，生存分析显示核周Ezrin表达模式的宫颈癌患者生存时间长于胞浆Ezrin表达模式的宫颈癌患者。因此，Ezrin代表了一个有希望的目标，为开发新的和有效的策略，旨在预防宫颈癌的进展。
Cervical cancer is the third most common cancer in females worldwide. The treatment options for advanced cervical cancer are limited, leading to high mortality. Ezrin is a membrane-cytoskeleton-binding protein recently reported to act as a tumor promoter, and we previously indicated that the aberrant localization and overexpression of Ezrin could be an independent effective biomarker for prognostic evaluation of cervical cancers. In this study, we identified Ezrin as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in cervical cancer. Ezrin knock-down inhibited anchorage-independent growth, cell migration, and invasion of cervical cancer cell lines in vitro and in vivo. EMT was inhibited in Ezrin-depleted cells, with up-regulation of E-cadherin and Cytokeratin-18 (CK-18) and down-regulation of mesenchymal markers. Ezrin knock-down also induced Akt phosphorylation. These results implicate Ezrin as an EMT regulator and tumor promoter in cervical cancer, and down-regulation of Ezrin suppressed cervical cancer progression, possibly via the phosphoinositide 3-kinase/Akt pathway. Furthermore, the expression pattern of Ezrin protein was closely related with the lymphovascular invasion status of cervical cancer by immunohistochemistry, and the survival analysis revealed that the cervical cancer patients with the perinuclear Ezrin expression pattern had longer survival time than those with the cytoplasmic Ezrin expression pattern. Ezrin thus represents a promising target for the development of novel and effective strategies aimed at preventing the progression of cervical cancer.