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Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
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Deubiquitinase USP35 restrains STING-mediated interferon signaling in ovarian cancer

Jiawen Zhang1,2, Yunfei Chen1, Xianfei Chen1

  • 1Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Cell Death and Differentiation
|July 18, 2020
PubMed

Insights

USP35 deubiquitinase is upregulated in ovarian cancer, inactivating the STING pathway. Reducing USP35 enhances anti-tumor immunity and sensitizes cells to cisplatin, revealing USP35 as a therapeutic target for ovarian cancer.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Ovarian cancer is a lethal malignancy with limited treatment options.
  • The STING pathway is crucial for anti-tumor immunity but often inactivated in cancers.
  • Understanding mechanisms of STING inactivation is vital for developing new ovarian cancer therapies.

Purpose of the Study:

  • To investigate the role of deubiquitinase USP35 in ovarian cancer.
  • To elucidate the mechanism by which USP35 affects the STING pathway.
  • To evaluate USP35 as a potential therapeutic target in ovarian cancer.

Main Methods:

  • Analysis of USP35 expression in ovarian cancer tissues.
  • Investigating the effect of USP35 silencing on STING pathway activation.
  • Assessing USP35's interaction with STING.
  • Evaluating the impact of USP35 knockdown on cisplatin sensitivity.

Main Results:

  • USP35 is upregulated in ovarian cancer and correlates with poor prognosis and reduced CD8+ T cell infiltration.
  • Silencing USP35 reactivates the STING-TBK1-IRF3 pathway, increasing type I interferon production.
  • USP35 directly deubiquitinates and inactivates STING.
  • USP35 knockdown sensitizes ovarian cancer cells to cisplatin.

Conclusions:

  • Upregulated USP35 contributes to STING pathway inactivation in ovarian cancer.
  • USP35 represents a potential therapeutic target to enhance anti-tumor immunity and chemosensitivity in ovarian cancer.

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