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Ras association domain family member 10 suppresses gastric cancer growth by cooperating with GSTP1 to regulate

X Li1,2, Q Liang1, W Liu3

  • 1Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.

Oncogene
|August 18, 2015
PubMed

Insights

Ras association domain family 10 (RASSF10) acts as a tumor suppressor in gastric cancer by inhibiting cell growth and promoting apoptosis. Promoter methylation of RASSF10 is linked to poor patient survival, highlighting its clinical significance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Ras association domain family (RASSF) includes tumor suppressors.
  • The role of RASSF10 in gastric cancer (GC) requires investigation.

Purpose of the Study:

  • To investigate the biological function of RASSF10 in GC.
  • To determine the clinical implication of RASSF10 in GC.

Main Methods:

  • Assessed RASSF10 expression and promoter methylation in GC cell lines and tissues.
  • Utilized The Cancer Genome Atlas (TCGA) for correlation analysis.
  • Performed in vitro and in vivo functional assays upon RASSF10 re-expression or knockdown.
  • Identified downstream effectors using co-immunoprecipitation and mass spectrometry.

Main Results:

  • RASSF10 was silenced in GC via promoter methylation, negatively correlating with mRNA expression.
  • RASSF10 re-expression suppressed GC cell viability, migration, invasion, and tumorigenicity, while inducing apoptosis.
  • RASSF10 directly cooperated with glutathione S-transferase Pi 1 (GSTP1) to regulate the JNK/c-Jun/AP-1 pathway.
  • RASSF10 methylation was frequent in GC and an independent predictor of poor survival.

Conclusions:

  • RASSF10 functions as a tumor suppressor in GC.
  • RASSF10 exerts its function partly through the GSTP1-mediated regulation of the JNK/c-Jun/AP-1 pathway.
  • RASSF10 promoter methylation serves as a prognostic biomarker for GC patients.

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