2. Academic Validation
  3. Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

  • Cell Death Dis. 2020 Jul 9;11(7):520. doi: 10.1038/s41419-020-2725-4.
Yifan Wang 1 2 3,  Ruocen Liao 1 3,  Xingyu Chen 1 3,  Xuhua Ying 2,  Guanping Chen 2,  Mingqian Li 2,  Chenfang Dong 4 5
Affiliations

Affiliations

  • 1 Department of Pathology and Pathophysiology, and Department of Surgical Oncology (breast center) of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Cancer Institute of Integrative Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China.
  • 3 Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Department of Pathology and Pathophysiology, and Department of Surgical Oncology (breast center) of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. chenfangdong@zju.edu.cn.
  • 5 Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou, China. chenfangdong@zju.edu.cn.
PMID: 32647142 DOI: 10.1038/s41419-020-2725-4
Abstract

Breast Cancer is considered to be the most prevalent Cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated Receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of Cancer cells. However, the functions and underlying mechanisms of PAR1 in breast Cancer remain unclear. In this study, we found that PAR1 is highly expressed in high invasive breast Cancer cells, and predicts poor prognosis in ER-negative and high-grade breast Cancer patients. Mechanistically, Twist transcriptionally induces PAR1 expression, leading to inhibition of Hippo pathway and activation of YAP/TAZ; Inhibition of PAR1 suppresses YAP/TAZ-induced epithelial-mesenchymal transition (EMT), invasion, migration, Cancer stem cell (CSC)-like properties, tumor growth and metastasis of breast Cancer cells in vitro and in vivo. These findings suggest that PAR1 acts as a direct transcriptionally target of Twist, can promote EMT, tumorigenicity and metastasis by controlling the Hippo pathway; this may lead to a potential therapeutic target for treating invasive breast Cancer.

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