G-protein-coupled estrogen receptor suppresses the migration of osteosarcoma cells via post-translational regulation of Snail
- 116 Downloads
Emerging evidences show that G-protein-coupled estrogen receptor (GPER) can regulate the progression of various cancers, while its roles in the progression of osteosarcoma (OS) are not well illustrated.
The expression of GPER in OS cells and tissues were checked. Its roles in cell migration and expression of Snail was checked by use of its agonist G-1.
We found that the expression of GPER in OS cells and tissues were lower than that in their corresponding controls. OS patients with higher levels of GPER showed increased overall survival rate (OS) as compared with the lower ones. The activator of GPER (G-1) or overexpression of GPER can inhibit the migration and invasion of OS cells and downregulate mesenchymal markers. G-1 can rapidly decrease the expression of Snail, one powerful epithelial–mesenchymal transition transcription factor (EMT-TF). Overexpression of Snail can attenuate the suppression effects of G-1 on migration of OS cells, suggesting that Snail was involved in GPER-regulated migration of OS cells. Mechanically, G-1 rapidly decreased the protein of Snail but had no effect on its mRNA expression. This was because G-1 can decrease the protein stability of Snail. Further, G-1 increased the expression of FBXL5, which can trigger the proteasome-mediated degradation of Snail. Knockdown of FBXL5 can reverse G-1-induced downregulation of Snail in OS cells.
Activation of GPER can suppress the migration and invasion of OS cells via FBXL5-mediated post-translational down regulation of Snail. It suggested that targeted activation of GPER might be a potent potential therapy approach to overcome the metastasis of OS patients.
KeywordsGPER Snail EMT Osteosarcoma FBXL5
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
Research involving human participants and/or animals
No human or animal study.
Informed consent was obtained from all individual participants included in the study.
- Chen P, Wang H, Duan Z, Zou JX, Chen H, He W, Wang J (2014) Estrogen-related receptor alpha confers methotrexate resistance via attenuation of reactive oxygen species production and P53 mediated apoptosis in osteosarcoma cells. Biomed Res Int 2014:616025Google Scholar
- Fang D, Yang H, Lin J, Teng Y, Jiang Y, Chen J, Li Y (2015) 17beta-estradiol regulates cell proliferation, colony formation, migration, invasion and promotes apoptosis by upregulating miR-9 and thus degrades MALAT-1 in osteosarcoma cell MG-63 in an estrogen receptor-independent manner. Biochem Biophys Res Commun 457:500–506CrossRefGoogle Scholar
- Filardo EJ, Quinn JA, Bland KI, Frackelton AR Jr (2000) Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol (Baltim MD) 14:1649–1660CrossRefGoogle Scholar
- Meng X, Zhu Y, Tao L, Zhao S, Qiu S (2018) miR-590-3p mediates melatonin-induced cell apoptosis by targeting septin 7 in the human osteoblast cell line hFOB 1.19. Mol Med Rep 17:7202–7208Google Scholar