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

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 can...

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Bibliographic Details
Published in:	Nature communications 2018-05, Vol.9 (1), p.1920-13, Article 1920
Main Authors:	Kang, Myoung-Hee, Choi, Hyunji, Oshima, Masanobu, Cheong, Jae-Ho, Kim, Seokho, Lee, Jung Hoon, Park, Young Soo, Choi, Hueng-Sik, Kweon, Mi-Na, Pack, Chan-Gi, Lee, Ju-Seog, Mills, Gordon B, Myung, Seung-Jae, Park, Yun-Yong
Format:	Article
Language:	eng
Subjects:	Animals Cancer Cell Line, Tumor Estrogens Female Gamma function Gene expression Gene Expression Regulation, Neoplastic Genes Genes, Tumor Suppressor Humans Male Mice Receptors, Estrogen - genetics Receptors, Estrogen - metabolism Signaling Stomach cancer Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Target recognition Therapeutic applications Transcription Factor 4 - genetics Transcription Factor 4 - metabolism Tumors Wnt Signaling Pathway
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Summary:	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.
ISSN:	2041-1723 2041-1723