Estrogen-related Receptor Gamma Functions As a Tumor Suppressor in Gastric Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2018 May 17

PMID 29765046

Citations 56

Authors

Myoung-Hee Kang

Hyunji Choi

Masanobu Oshima

Jae-Ho Cheong

Seokho Kim

Jung Hoon Lee

Young Soo Park

Hueng-Sik Choi

Mi-Na Kweon

Chan-Gi Pack

Ju-Seog Lee

Gordon B Mills

Seung-Jae Myung

Yun-Yong Park

Affiliations

Soon will be listed here.

Abstract

The principle factors underlying gastric cancer (GC) development and outcomes are not well characterized resulting in a paucity of validated therapeutic targets. To identify potential molecular targets, we analyze gene expression data from GC patients and identify the nuclear receptor ESRRG as a candidate tumor suppressor. ESRRG expression is decreased in GC and is a predictor of a poor clinical outcome. Importantly, ESRRG suppresses GC cell growth and tumorigenesis. Gene expression profiling suggests that ESRRG antagonizes Wnt signaling via the suppression of TCF4/LEF1 binding to the CCND1 promoter. Indeed, ESRRG levels are found to be inversely correlated with Wnt signaling-associated genes in GC patients. Strikingly, the ESRRG agonist DY131 suppresses cancer growth and represses the expression of Wnt signaling genes. Our present findings thus demonstrate that ESRRG functions as a negative regulator of the Wnt signaling pathway in GC and is a potential therapeutic target for this cancer.

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