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

Nature Communications
Myoung-Hee KangYun-Yong Park

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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Citations

Jul 13, 2019·Journal of Cellular Biochemistry·Xi ChenEnjian Shen
Aug 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takashi TanidaMasaki Tanaka
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May 26, 2021·Computers in Biology and Medicine·Vahid GhafarpourAli Masoudi-Nejad
Jun 1, 2021·Biochemical and Biophysical Research Communications·Myoung-Hee KangYun-Yong Park

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Datasets Mentioned

BETA
GSE29272
GSE13861
GSE14208
GSE62254
38
GSE78050

Methods Mentioned

BETA
PCR
xenograft
transfection
ELISA
ubiquitination
immunoprecipitation
ChIP
fluorescence cross-correlation spectroscopy
chips
Fluorescence

Software Mentioned

ZEN2012
R
Linear Models for Microarray Data
ZEN
ArrayTools
BRB array

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