Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2

  1. Yibin Kang1
  1. 1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA;
  2. 2Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
  3. 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  1. Corresponding author: ykang{at}princeton.edu
  • Present addresses: 4Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; 5School of Medicine, Tsinghua University, Beijing 100084, China.

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.

Keywords

Footnotes

  • Received April 27, 2020.
  • Accepted August 7, 2020.

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