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

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 Mills, Seung Jae Myung, Yun Yong Park

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Article number1920
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Kang, M. H., Choi, H., Oshima, M., Cheong, J. H., Kim, S., Lee, J. H., Park, Y. S., Choi, H. S., Kweon, M. N., Pack, C. G., Lee, J. S., Mills, G., Myung, S. J., & Park, Y. Y. (2018). Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer. Nature Communications, 9(1), [1920]. https://doi.org/10.1038/s41467-018-04244-2