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Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer

Myoung-Hee Kang1,2,3, Hyunji Choi4, Masanobu Oshima5

  • 1ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.

Nature Communications
|May 17, 2018
PubMed

Insights

Estrogen-related receptor gamma (ESRRG) acts as a tumor suppressor in gastric cancer (GC) by inhibiting Wnt signaling. Targeting ESRRG may offer a new therapeutic strategy for GC patients.

Area of Science:

  • Molecular oncology
  • Cancer biology
  • Gastrointestinal oncology

Background:

  • Gastric cancer (GC) development and outcomes are poorly understood, with limited validated therapeutic targets.
  • Identifying novel molecular targets is crucial for improving GC treatment strategies.

Purpose of the Study:

  • To identify potential molecular targets for gastric cancer.
  • To investigate the role of the nuclear receptor ESRRG in gastric cancer development and progression.

Main Methods:

  • Analysis of gene expression data from gastric cancer patients.
  • Functional assays to assess ESRRG's effect on GC cell growth and tumorigenesis.
  • Gene expression profiling to elucidate ESRRG's mechanism of action.
  • Correlation analysis of ESRRG expression with Wnt signaling pathway markers.

Main Results:

  • ESRRG expression is significantly decreased in gastric cancer tissues and correlates with poor clinical outcomes.
  • ESRRG suppresses gastric cancer cell proliferation and tumorigenesis.
  • ESRRG antagonizes the Wnt signaling pathway by inhibiting TCF4/LEF1 binding to the CCND1 promoter.
  • ESRRG expression is inversely correlated with Wnt signaling-associated genes in GC patients.
  • The ESRRG agonist DY131 demonstrated anti-tumor effects by suppressing cancer growth and Wnt signaling.

Conclusions:

  • ESRRG functions as a tumor suppressor in gastric cancer.
  • ESRRG negatively regulates the Wnt signaling pathway in GC.
  • ESRRG represents a potential therapeutic target for gastric cancer treatment.

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