Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2

Genes Dev. 2020 Oct 1;34(19-20):1310-1315. doi: 10.1101/gad.339804.120. Epub 2020 Sep 17.

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: SLUG; SNAI2; USP20; deubiquitinase; invasion; metastasis; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / physiopathology*
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Library
  • Humans
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics*
  • Protein Stability
  • Proteolysis
  • RNA, Small Interfering / metabolism
  • Snail Family Transcription Factors / metabolism*
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitination

Substances

  • RNA, Small Interfering
  • SNAI2 protein, human
  • Snail Family Transcription Factors
  • USP20 protein, human
  • Ubiquitin Thiolesterase