Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2
- Wenyang Li1,4,
- Minhong Shen1,
- Yi-Zhou Jiang2,3,
- Ruina Zhang1,
- Hanqiu Zheng1,5,
- Yong Wei1,
- Zhi-Ming Shao2,3 and
- Yibin Kang1
- 1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA;
- 2Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Corresponding author: ykang{at}princeton.edu
Abstract
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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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.339804.120.
- Received April 27, 2020.
- Accepted August 7, 2020.
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