Related Experiment Video

Updated: Sep 13, 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

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Oxytocin Receptor Regulates the Hippo/YAP Axis to Drive Hepatocarcinogenesis

Huijie Yang1,2, Jiayao Cui1,2, Peng Su3

  • 1Xinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, P.R. China.

Cancer Research
|July 31, 2025
PubMed

Insights

Dysregulation of the Hippo-YAP pathway drives liver cancer. Researchers identified the oxytocin receptor (OXTR) as a key activator, finding its antagonist, atosiban, effectively inhibits hepatocellular carcinoma (HCC) growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hippo signaling pathway dysregulation, particularly YAP, is a key driver of hepatocellular carcinoma (HCC).
  • Targeting the Hippo pathway offers potential therapeutic strategies for improving HCC patient survival.

Purpose of the Study:

  • To identify G-protein coupled receptors (GPCRs) associated with the Hippo/YAP pathway in HCC.
  • To investigate the role of the oxytocin receptor (OXTR) in HCC progression and its potential as a therapeutic target.

Main Methods:

  • Unbiased siRNA screen of US-approved GPCR-targeted drugs.
  • Correlation analysis of OXTR expression with Hippo gene signature and patient survival.
  • In vivo and in vitro functional assays using xenograft, patient-derived explant, organoid, and mouse models.
  • Molecular analyses including YAP dephosphorylation, nuclear accumulation, and transcriptional activity assays.
  • Investigation of OXTR interaction with Gαq/11 and downstream signaling (ROCK/LATS axis).
  • Chromatin immunoprecipitation (ChIP) assays to assess YAP binding to OXTR enhancer regions.

Main Results:

  • OXTR was identified as a significant activator of the Hippo/YAP axis in HCC.
  • OXTR expression correlated with poor survival outcomes in HCC patients.
  • The OXTR antagonist atosiban demonstrated efficacy in inhibiting HCC growth across multiple preclinical models.
  • OXTR activation promotes HCC progression by facilitating YAP dephosphorylation and nuclear accumulation via the Gαq/11/ROCK/LATS pathway.
  • A positive feedback loop exists where YAP enhances OXTR transcription.

Conclusions:

  • The oxytocin receptor (OXTR) plays a critical role in hepatocarcinogenesis by activating the Hippo/YAP pathway.
  • Inhibition of OXTR using atosiban represents a promising therapeutic strategy for hepatocellular carcinoma (HCC).

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