OTUB1 promotes esophageal squamous cell carcinoma metastasis through modulating Snail stability

被引：86
作者：
Zhou, Honghong [1 ,2 ,3 ]
Liu, Yongshuo [1 ,2 ]
Zhu, Rui [1 ,2 ]
Ding, Fang [1 ,2 ]
Cao, Xiufeng [4 ]
Lin, Dongxin [1 ,2 ,3 ]
Liu, Zhihua [1 ,2 ]
机构：
[1] Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, State Key Lab Mol Oncol, Beijing, Peoples R China
[2] Peking Union Med Coll, Beijing, Peoples R China
[3] Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, Dept Etiol & Carcinogenesis, Beijing, Peoples R China
[4] Nanjing Med Univ, Nanjing Hosp 1, Dept Surg Oncol, Nanjing, Jiangsu, Peoples R China
来源：
ONCOGENE | 2018年 / 37卷 / 25期
基金：
美国国家科学基金会; 国家重点研发计划;
关键词：
EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR SNAIL; BREAST-CANCER; POOR-PROGNOSIS; DEGRADATION; INVASION; EMT; DEUBIQUITINATION; PROGRESSION; ENZYME;
D O I：
10.1038/s41388-018-0224-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Snail is a key regulator of epithelial-mesenchymal transition (EMT) and plays an important role in tumor progression and metastasis. Snail is rapidly degraded in the cells and its protein level is critically controlled. Although several E3 ligases regulating Snail degradation have been defined, the deubiquitinases (DUBs) responsible for Snail deubiquitination are less studied. We identified ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) as a DUB that stabilizes Snail through preventing its ubiquitination and proteasomal degradation. Functionally, OTUB1 facilitates metastasis of esophageal squamous cell carcinoma (ESCC) through promoting Snail protein stability. Moreover, OTUB1 is highly expressed in ESCC and higher expression of OTUB1 predicts poor prognosis. These findings suggest that OTUB1 is an essential regulator of Snail and plays a critical role in facilitating esophageal cancer progression.
引用
收藏
页码：3356 / 3368
页数：13
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