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Knockdown Proteomics Reveals USP7 as a Regulator of Cell-Cell Adhesion in Colorectal Cancer via AJUBA

Ahood Al-Eidan1, Ben Draper2, Siyuan Wang2

  • 1School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom; Department of Biology, College of Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Molecular & Cellular Proteomics : MCP
|November 10, 2024
PubMed

Insights

Ubiquitin-specific protease 7 (USP7) is crucial in colorectal cancer, regulating key pathways. This study identifies Ajuba protein as a USP7 partner, revealing its role in cell adhesion and potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-specific protease 7 (USP7) plays a role in various cancers, including colorectal cancer, by regulating Wnt signaling and the P53-MDM2 pathway.
  • USP7 is a promising therapeutic target for cancer due to the availability of small-molecule inhibitors.
  • Identifying USP7 interaction partners and substrates is essential for understanding its role in cancer.

Purpose of the Study:

  • To identify USP7-dependent proteins in a colorectal cancer cell model.
  • To investigate the interaction between USP7 and the Ajuba LIM domain protein.
  • To elucidate the role of the USP7-Ajuba interaction in colorectal cancer cell adhesion.

Main Methods:

  • Inducible knockdown of USP7 in a colorectal cancer cell model.
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantitative proteomics.
  • Co-immunoprecipitation (Co-IP) to identify protein interactions.

Main Results:

  • USP7 knockdown significantly inhibited colorectal cancer cell viability, colony formation, and cell-cell adhesion.
  • The Ajuba LIM domain protein was identified as a USP7 interacting partner.
  • Knockdown of USP7 or Ajuba reduced cell-cell adhesion and affected adherens junction proteins.

Conclusions:

  • USP7 plays a significant role in colorectal cancer progression through its protein interaction networks.
  • The Ajuba protein is a component of USP7 protein networks in colorectal cancer and contributes to cell-cell adhesion.
  • Targeting the USP7-Ajuba interaction may offer a therapeutic strategy for colorectal cancer.
Keywords:
AJUBAUSP7cancerdeubiquitinaseinducible knock-down

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