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USP26 通过稳定 Snail 促进食管鳞状细胞癌转移。

USP26 promotes esophageal squamous cell carcinoma metastasis through stabilizing Snail.

机构信息

State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, PR China.

State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, PR China.

出版信息

Cancer Lett. 2019 Apr 28;448:52-60. doi: 10.1016/j.canlet.2019.02.007. Epub 2019 Feb 11.

DOI:10.1016/j.canlet.2019.02.007
PMID:30763716
Abstract

Snail is an important transcription factor of epithelial-mesenchymal transition (EMT) and related to poor prognosis and distant metastasis of tumor patients. Snail is a liable protein and degraded by ubiquitin-proteasome system. There are various E3 ligases mediating its degradation, but the deubiquitinating enzyme reversed Snail degradation is not fully understood. In this study, we screened a DUB library and found USP26 is a potent deubiquitinase mediating Snail stabilization. We also identified that USP26 is a booster of esophageal squamous cell carcinoma (ESCC) cell migration and invasion, and it is highly expressed in ESCC samples. Our observation demonstrates that USP26 is a novel deubiquitinating enzyme of Snail and it provides a potential target for the therapy of esophageal cancer metastasis.

摘要

蜗牛是上皮-间质转化(EMT)的重要转录因子,与肿瘤患者的预后不良和远处转移有关。蜗牛是一种易位蛋白,可被泛素-蛋白酶体系统降解。有多种 E3 连接酶介导其降解,但逆转蜗牛降解的去泛素化酶尚未完全阐明。在这项研究中,我们筛选了一个 DUB 文库,发现 USP26 是一种有效的去泛素化酶,可介导蜗牛的稳定。我们还发现 USP26 是食管鳞状细胞癌(ESCC)细胞迁移和侵袭的增强子,在 ESCC 样本中高度表达。我们的观察表明,USP26 是蜗牛的一种新型去泛素化酶,为治疗食管癌转移提供了一个潜在的靶点。

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