Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Genes Dev. 2020 Oct 1;34(19-20):1310-1315. doi: 10.1101/gad.339804.120. Epub 2020 Sep 17.
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.
SNAI2/SLUG，一种促进转移的转录因子，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 文库进行了全面的增益和失能筛选，并鉴定 USP20 为一种调节 SNAI2 泛素化和稳定性的去泛素化酶 (DUB)。对 USP20 的进一步研究表明，它在促进乳腺癌的迁移、侵袭和转移中发挥作用。USP20 与乳腺癌肿瘤样本中的 SNAI2 蛋白水平呈正相关，较高的 USP20 表达与 ER 阳性乳腺癌患者的不良预后相关。
