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- Title
Nuclear receptor estrogen-related receptor gamma suppresses colorectal cancer aggressiveness by regulating Wnt/β-catenin signaling.
- Authors
Guo, Xiaohong; Yue, Longtao; Li, Min; Dai, Ang; Sun, Junying; Fang, Lei; Zhao, Hai; Sun, Qing
- Abstract
Colorectal cancer (CRC) is the predominant cause of cancer-related death worldwide, because of the lack of effective therapeutic targets. Estrogen-related receptor gamma (ESRRG), which belongs to the family of nuclear receptors, functions as an important element regulating gene transcription. In our report, we identified ESRRG as a potential tumor suppressor. The decreased level of ESRRG was initially observed in CRC and was highly associated with a poor prognosis. ESRRG overexpression abrogated cell growth and metastasis in vitro and in vivo. Mechanistically, ESRRG repressed the epithelial-to-mesenchymal transition process and antagonized Wnt signaling by regulating β-catenin degradation. In addition, significant ESRRG hypermethylation was found in CRC and inversely correlated with its expression. Consistently, the expression of ESRRG was induced after treatment with DNA demethylating agent 5-aza-2ʹ-deoxycytidine. Taken together, these findings define a tumor-suppressive role of ESRRG in CRC, providing a potential novel therapeutic approach for this cancer.
- Subjects
COLORECTAL cancer; EPITHELIAL-mesenchymal transition; WNT signal transduction; THERAPEUTICS; NUCLEAR families
- Publication
Carcinogenesis, 2022, Vol 43, Issue 9, p865
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgac054