State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Oncogene. 2018 Jun;37(25):3356-3368. doi: 10.1038/s41388-018-0224-1. Epub 2018 Mar 21.
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.
蜗牛是上皮间质转化 (EMT) 的关键调节因子，在肿瘤进展和转移中发挥重要作用。蜗牛在细胞内迅速降解，其蛋白水平受到严格控制。尽管已经定义了几种调节蜗牛降解的 E3 连接酶，但负责蜗牛去泛素化的去泛素酶 (DUB) 研究较少。我们发现卵巢肿瘤结构域包含的泛素醛结合蛋白 1 (OTUB1) 是一种 DUB，通过防止其泛素化和蛋白酶体降解来稳定蜗牛。从功能上讲，OTUB1 通过促进蜗牛蛋白稳定性促进食管鳞状细胞癌 (ESCC) 的转移。此外，OTUB1 在 ESCC 中高表达，OTUB1 表达水平较高预示预后不良。这些发现表明，OTUB1 是蜗牛的重要调节因子，在促进食管癌进展中发挥关键作用。
