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Updated: Aug 3, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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USP1 modulates hepatocellular carcinoma progression via the Hippo/TAZ axis

Dongyi Liu1,2, Quanhui Li1, Yifeng Zang1

  • 1Department of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, P. R. China.

Cell Death & Disease
|April 11, 2023
PubMed

Insights

Hepatocellular carcinoma (HCC) progression is linked to USP1, which stabilizes TAZ by preventing its ubiquitylation. USP1 is a potential therapeutic target for HCC, impacting the Hippo signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally.
  • The Hippo signaling pathway, including YAP/TAZ, is crucial in suppressing liver cancer.
  • The ubiquitin‒proteasome system's role in Hippo signaling is an emerging area of research.

Purpose of the Study:

  • To investigate the role of deubiquitinase (DUB) enzymes in regulating Hippo signaling in HCC.
  • To identify novel regulators of the Hippo pathway and potential therapeutic targets for HCC.

Main Methods:

  • Conducted a deubiquitinase siRNA screen to identify regulators of Hippo signaling.
  • Analyzed The Cancer Genome Atlas (TCGA) data for USP1 expression in HCC.
  • Performed RNA sequencing and mechanistic assays to elucidate USP1's function.
  • Investigated USP1's interaction with TAZ and its effect on TAZ stability.

Main Results:

  • USP1 was identified as a critical regulator of Hippo signaling activity.
  • Elevated USP1 expression in HCC correlates with poor patient survival.
  • USP1 depletion impacts Hippo signaling and HCC cell line activity.
  • USP1 enhances TAZ stability by inhibiting its K11-linked polyubiquitination, promoting HCC progression.

Conclusions:

  • USP1 plays a key role in regulating the Hippo/TAZ axis in HCC.
  • USP1 stabilization of TAZ is a novel mechanism contributing to HCC pathogenesis.
  • USP1 represents a potential therapeutic target for hepatocellular carcinoma.

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