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Updated: Dec 15, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

Yifan Wang1,2,3, Ruocen Liao1,3, Xingyu Chen1,3

  • 1Department of Pathology and Pathophysiology, and Department of Surgical Oncology (breast center) of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Cell Death & Disease
|July 11, 2020
PubMed

Insights

Protease-activated receptor 1 (PAR1) drives breast cancer invasion and metastasis by activating YAP/TAZ signaling. Inhibiting PAR1 may offer a new therapeutic strategy for invasive breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Breast cancer is the most common cancer globally, with metastasis being the leading cause of mortality.
  • Protease-activated receptor 1 (PAR1), a G protein-coupled receptor, is implicated in cancer cell invasion and metastasis, but its specific role in breast cancer is not fully understood.

Purpose of the Study:

  • To investigate the role and mechanism of PAR1 in breast cancer progression, focusing on its relationship with the Hippo pathway and epithelial-mesenchymal transition (EMT).

Main Methods:

  • Analysis of PAR1 expression in breast cancer cells and patient data.
  • Investigating the transcriptional regulation of PAR1 by Twist.
  • Examining the effects of PAR1 inhibition on Hippo pathway signaling (YAP/TAZ), EMT, cancer stem cell properties, and metastasis in vitro and in vivo.

Main Results:

  • PAR1 is highly expressed in invasive breast cancer cells and correlates with poor prognosis in specific patient subgroups (ER-negative, high-grade).
  • Twist directly induces PAR1 expression, which in turn inhibits the Hippo pathway, leading to YAP/TAZ activation.
  • Inhibition of PAR1 suppressed YAP/TAZ-driven EMT, invasion, migration, cancer stem cell characteristics, tumor growth, and metastasis.

Conclusions:

  • PAR1 is a direct transcriptional target of Twist and promotes breast cancer invasion, tumorigenicity, and metastasis by modulating the Hippo pathway.
  • PAR1 represents a potential therapeutic target for treating invasive breast cancer.

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