Loss of Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) inhibits the progression of ovarian cancer in coordination with ubiquitin-specific protease 10 (USP10)

Bioengineered. 2022 Jan;13(1):721-734. doi: 10.1080/21655979.2021.2012624.

Abstract

Ovarian cancer (OC) is one of the most lethal gynecological malignancies. However, the molecular mechanisms underlying the development of OC remain unclear. Here, we report that loss of Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) inhibits the progression of OC cells. Analysis of databases and clinical specimens showed that G3BP1 is upregulated in OC. The Kaplan-Meier plot results showed that G3BP1 is highly expressed in OC with a poor clinical outcome. Moreover, loss-of-G3BP1 suppresses the proliferation, migration, and invasion of OC cells. Protein-protein interaction network analysis and immunoprecipitation assay showed that ubiquitin-specific protease 10 (USP10) interacts with G3BP1. We next found that USP10 coordinately promotes tumor progression with G3BP1. Moreover, loss of USP10could restore the G3BP1-induced proliferation, migration, and invasion of OC cells. These data indicate that G3BP1 coordinated with USP10 to facilitate the progression of OC cells, and that G3BP1 may become a treatment target for OC.

Keywords: G3BP1; Ovarian cancer; USP10; invasion; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Female
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Recognition Motif Proteins / genetics
  • RNA Recognition Motif Proteins / metabolism*
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • Neoplasm Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • USP10 protein, human
  • Ubiquitin Thiolesterase
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases

Grants and funding

This work was supported by the Natural Science Foundation of Chongqing, China (cstc2020jcyj-msxmX0344).