Related Experiment Video

Updated: Sep 5, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.0K

DUB1 suppresses Hippo signaling by modulating TAZ protein expression in gastric cancer

Dehai Wang1, Zhongbo Li2, Xin Li2

  • 1Department of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong Province, People's Republic of China.

Journal of Experimental & Clinical Cancer Research : CR
|July 12, 2022
PubMed
Abstract

Insights

Deubiquitinase DUB1 activates TAZ protein, promoting gastric cancer stemness and progression. DUB1 is a potential therapeutic target for Hippo-driven gastric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The Hippo pathway is a tumor suppressor pathway frequently dysregulated in cancers.
  • YAP/TAZ protein activity is regulated by phosphorylation, but their activation in cancer despite Hippo pathway activation remains unclear.
  • Posttranslational modifications, including ubiquitination, are increasingly recognized for their role in TAZ function modulation.

Purpose of the Study:

  • To investigate the role of deubiquitinases (DUBs) in gastric cancer progression.
  • To identify novel regulators of TAZ protein activity in the context of the Hippo pathway.
  • To explore potential therapeutic targets for Hippo-driven gastric cancer.

Main Methods:

  • Screening of a deubiquitinase siRNA library in gastric cancer cell lines.
  • Western blot analysis, real-time PCR, immunoprecipitation, and in vitro ubiquitination assays.
  • Establishment of a gastric cancer xenograft mouse model.

Main Results:

  • Deubiquitinase 1 (DUB1) was identified as a critical modulator of gastric cancer stemness and progression.
  • DUB1 deubiquitinates and activates the TAZ protein, leading to its stabilization.
  • Elevated DUB1 expression in gastric cancer correlates with TAZ activation and poor patient survival.

Conclusions:

  • DUB1 is a novel deubiquitinase that functions within the Hippo/TAZ signaling axis.
  • DUB1-mediated TAZ activation plays a significant role in gastric cancer.
  • DUB1 represents a potential therapeutic target for gastric cancer treatment.
Keywords:
DUB1DeubiquitinationGastric cancerStabilizeTAZ

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