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

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  • Myoung-Hee Kang

    (University of Ulsan College of Medicine
    University of Ulsan College of Medicine
    MD Anderson Cancer Center)

  • Hyunji Choi

    (Dong-A University)

  • Masanobu Oshima

    (Kanazawa University)

  • Jae-Ho Cheong

    (Yonsei University College of Medicine)

  • Seokho Kim

    (Korea Research Institute of Bioscience and Biotechnology)

  • Jung Hoon Lee

    (University of Ulsan College of Medicine)

  • Young Soo Park

    (University of Ulsan College of Medicine)

  • Hueng-Sik Choi

    (Chonnam National University)

  • Mi-Na Kweon

    (University of Ulsan College of Medicine)

  • Chan-Gi Pack

    (University of Ulsan College of Medicine
    University of Ulsan College of Medicine)

  • Ju-Seog Lee

    (MD Anderson Cancer Center)

  • Gordon B. Mills

    (MD Anderson Cancer Center)

  • Seung-Jae Myung

    (University of Ulsan College of Medicine
    University of Ulsan College of Medicine
    University of Ulsan College of Medicine)

  • Yun-Yong Park

    (University of Ulsan College of Medicine
    University of Ulsan College of Medicine)

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.

Suggested Citation

  • 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 , 2018. "Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04244-2
    DOI: 10.1038/s41467-018-04244-2
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