Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2.

Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2.
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DOI:
10.1101/gad.339804.120
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发表时间:
2020-10-01
影响因子:
10.5
通讯作者:
Kang Y
Kang Y
中科院分区:
生物学1区
文献类型:
--
作者:
Li W;Shen M;Jiang YZ;Zhang R;Zheng H;Wei Y;Shao ZM;Kang Y

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在这项研究中,Li等人使用65个基因的人DUB cDNA文库和98个基因的siRNA文库进行了全面的功能获得和功能丧失筛选,并将USP 20鉴定为调节转移促进转录因子SNAI 2、泛素化和稳定性的去泛素化酶(DUB)。SNAI 2/SLUG是一种转移促进转录因子,是一种不稳定的蛋白质,通过泛素蛋白酶体降解系统降解。在这里,我们使用65个基因的人DUB cDNA文库和98个基因的siRNA文库进行了全面的功能获得和功能丧失筛选,并将USP 20鉴定为调节SNAI 2泛素化和稳定性的去泛素化酶(DUB)。进一步的研究表明USP 20在促进乳腺癌的迁移、侵袭和转移中发挥作用。在乳腺肿瘤样本中,USP 20与SNAI 2蛋白水平呈正相关,USP 20的高表达与ER-乳腺癌患者的预后不良相关。
In this study, Li et al. conducted comprehensive gain- and loss-of-function screens using a human DUB cDNA library of 65 genes and an siRNA library of 98 genes, and identified USP20 as a deubiquitinase (DUB) that regulates a metastasis-promoting transcription factor, SNAI2, ubiquitination, and stability. SNAI2/SLUG, a metastasis-promoting transcription factor, is a labile protein that is degraded through the ubiquitin proteasome degradation system. Here, we conducted comprehensive gain- and loss-of-function screens using a human DUB cDNA library of 65 genes and an siRNA library of 98 genes, and identified USP20 as a deubiquitinase (DUB) that regulates SNAI2 ubiquitination and stability. Further investigation of USP20 demonstrated its function in promoting migration, invasion, and metastasis of breast cancer. USP20 positively correlates with SNAI2 protein level in breast tumor samples, and higher USP20 expression is associated with poor prognosis in ER− breast cancer patients.
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