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Decreased expression of protease-activated receptor 4 in human gastric cancer

Yong Zhang1, Guoyu Yu, Ping Jiang

  • 1Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao Chang Road, Kunming, Yunnan 650223, China. zhangy@mail.kiz.ac.cn

The International Journal of Biochemistry & Cell Biology
|June 4, 2011
PubMed

Insights

Protease-activated receptor 4 (PAR4) is downregulated in gastric cancer, correlating with aggressive disease. Promoter hypermethylation likely causes this loss of PAR4 expression.

Area of Science:

  • G-protein coupled receptor signaling
  • Cancer biology
  • Molecular oncology

Background:

  • Protease-activated receptors (PARs) are GPCRs with known roles in various cancers.
  • PAR4 is overexpressed in colon and prostate cancers.
  • PAR4's role in gastric cancer remained uninvestigated despite its presence in normal stomach tissue.

Purpose of the Study:

  • To investigate the expression and role of PAR4 in gastric cancer.
  • To determine if PAR4 expression is altered in gastric tumors compared to normal tissue.
  • To explore the potential mechanism of PAR4 down-regulation in gastric cancer.

Main Methods:

  • Quantitative real-time PCR (n=28) and tissue microarrays (n=74) to assess PAR4 expression.
  • Analysis of PAR4 localization in normal gastric mucosa.
  • Assessment of PAR4 promoter methylation using 5-aza-2'-deoxycytidine treatment and bisulfite sequencing in gastric and colon cancer cell lines.

Main Results:

  • PAR4 expression was significantly decreased in gastric cancer tissues compared to matched non-cancerous tissues.
  • Reduced PAR4 expression correlated with advanced disease features, including lymph node positivity and low differentiation.
  • PAR4 promoter hypermethylation was observed in gastric cancer cell lines lacking PAR4 expression, which was reversed by demethylating agents.

Conclusions:

  • Down-regulation of PAR4 is frequent in gastric cancers and associated with aggressive phenotypes.
  • Hypermethylation of the PAR4 promoter is a likely mechanism for the loss of PAR4 expression in gastric cancer.
  • PAR4 may serve as a potential biomarker or therapeutic target in gastric cancer.

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