Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer

Biomed Pharmacother. 2024 Apr:173:116323. doi: 10.1016/j.biopha.2024.116323. Epub 2024 Feb 23.

Abstract

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are essential elements of the deubiquitinase family, and are overexpressed in gastric cancer (GC). Through the regulation of several signaling pathways, such as Wnt/β-Catenin and nuclear factor-κB signaling, and the promotion of the expression of deubiquitination- and stabilization-associated proteins, USPs promote the proliferation, metastasis, invasion, and epithelial-mesenchymal transition of GC. In addition, the expression of USPs is closely related to clinicopathological features, patient prognosis, and chemotherapy resistance. USPs therefore could be used as prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they have not yet been tested in the clinic. This article provides an overview of the latest fundamental research on USPs in GC, aiming to enhance the understanding of how USPs contribute to GC progression, and identifying possible targets for GC treatment to improve patient survival.

Keywords: Deubiquitination; Gastric cancer; Inhibitors; Ubiquitin-specific proteases.

Publication types

  • Review

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Signal Transduction
  • Stomach Neoplasms* / metabolism
  • Ubiquitin-Specific Proteases / metabolism
  • Wnt Signaling Pathway

Substances

  • Ubiquitin-Specific Proteases