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

  • Nat Commun. 2018 May 15;9(1):1920. doi: 10.1038/s41467-018-04244-2.
Myoung-Hee Kang  1  2  3 ,  Hyunji Choi  4 ,  Masanobu Oshima  5 ,  Jae-Ho Cheong  6 ,  Seokho Kim  7 ,  Jung Hoon Lee  8 ,  Young Soo Park  9 ,  Hueng-Sik Choi  10 ,  Mi-Na Kweon  2 ,  Chan-Gi Pack  1  2 ,  Ju-Seog Lee  3 ,  Gordon B Mills  3 ,  Seung-Jae Myung  11  12  13 ,  Yun-Yong Park  14  15
Affiliations
  • 1. ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
  • 2. Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
  • 3. Department of Systems Biology, MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • 4. Department of Biological Sciences, Dong-A University, Busan, 49315, Republic of Korea.
  • 5. Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, 920-8641, Japan.
  • 6. Department of Surgery, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • 7. Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
  • 8. Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
  • 9. Department of Pathology, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
  • 10. National Creative Research Initiatives Center for Nuclear Receptor Signals and Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea.
  • 11. ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. [email protected].
  • 12. Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. [email protected].
  • 13. Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. [email protected].
  • 14. ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. [email protected].
  • 15. Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. [email protected].
PMID: 29765046 DOI: 10.1038/s41467-018-04244-2
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.