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USP12 facilitates gastric cancer progression via stabilizing YAP

Peng Zhang1, Dongyi Liu2, Yifeng Zang1

  • 1Department of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, Shandong, PR China.

Cell Death Discovery
|April 11, 2024
PubMed

Insights

Dysregulated Hippo signaling drives gastric cancer. Researchers identified USP12 as a key deubiquitinase promoting cancer progression by stabilizing YAP. Blocking USP12 may offer a new therapeutic strategy for gastric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hippo signaling pathway dysregulation is a key driver of gastric cancer progression.
  • Targeting the Hippo/YAP axis presents a promising therapeutic strategy, but effective drugs are lacking.
  • Ubiquitination modifications significantly influence Hippo/YAP signaling and cancer development.

Purpose of the Study:

  • To identify novel therapeutic targets and mechanisms to inhibit the Hippo/YAP axis in gastric cancer.
  • To investigate the role of deubiquitinases in regulating the Hippo/YAP pathway in gastric cancer.

Main Methods:

  • Screening of a deubiquitinase small interfering RNA library.
  • Bioinformatic analysis of patient data and gene expression.
  • Immunostaining and immunoprecipitation assays to determine protein localization and interaction.
  • Western blotting to assess protein ubiquitination levels.

Main Results:

  • USP12 was identified as a critical deubiquitinase involved in gastric cancer progression.
  • USP12 depletion inhibited gastric cancer growth, while overexpression promoted it.
  • USP12 localizes to the nucleus, interacts with YAP, and enhances its stability by inhibiting K48-linked poly-ubiquitination at the K315 site.
  • USP12 expression correlates with poor survival and YAP target gene activity in gastric cancer.

Conclusions:

  • USP12 is a novel regulator of the Hippo/YAP signaling pathway in gastric cancer.
  • USP12 promotes gastric cancer progression by stabilizing YAP.
  • Inhibition of USP12 represents a potential therapeutic strategy for gastric cancer treatment.

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