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USP20 mediates malignant phenotypic changes in bladder cancer through direct interactions with YAP1

Wensun Chen1, Siqi Wu1, Yifan Chen1

  • 1Department of Urology, Huashan Hospital Fudan University Shanghai, PR China.

Neoplasia (New York, N.Y.)
|December 14, 2024
PubMed

Insights

USP20 deubiquitinase stabilizes YAP1 protein, promoting bladder cancer progression. This finding reveals USP20 as a key regulator of the Hippo-YAP1 pathway in bladder cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The Hippo-YAP1 pathway is crucial in cancer, with its inhibition driving bladder cancer (BC) progression.
  • The Hippo pathway's activity is modulated by phosphorylation and ubiquitination of its components.
  • Deubiquitinases (DUBs) and E3 ligases co-regulate Hippo pathway protein ubiquitination.

Purpose of the Study:

  • To identify novel deubiquitinases regulating the Hippo-YAP1 pathway in bladder cancer.
  • To investigate the role of USP20 in the context of bladder cancer and the Hippo-YAP1 pathway.

Main Methods:

  • siRNA screening to identify potential DUBs.
  • Deubiquitinase overexpression assays.
  • Western blotting to assess protein levels and ubiquitination.
  • Tissue microarray analysis to evaluate USP20 expression in tumor tissues.
  • Co-immunoprecipitation to confirm protein interactions.

Main Results:

  • USP20 was identified as a deubiquitinase involved in the Hippo-YAP1 pathway.
  • USP20 directly regulates YAP1 expression and its downstream targets (CTGF, CYR61).
  • USP20 expression is elevated in bladder tumor tissues and correlates with YAP1 expression.
  • USP20 interacts with YAP1 and enhances its stability by inhibiting K48-linked poly-ubiquitination.

Conclusions:

  • USP20 functions as a deubiquitinase that stabilizes YAP1 protein.
  • USP20 plays a significant role in regulating the Hippo-YAP1 pathway in bladder cancer.
  • USP20 represents a potential therapeutic target for bladder cancer treatment.
Keywords:
Bladder cancerMalignant phenotypeUSP20YAP1deubiquitinase

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