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G-protein-coupled estrogen receptor suppresses the migration of osteosarcoma cells via post-translational regulation of Snail

  • Original Article – Cancer Research
  • Published:
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Authors and Affiliations

  1. Department of Orthopaedics, Henan Provincial People’s Hospital, Zhengzhou, 450003, China

    Zhen Wang, Xiao Chen, Yongqiang Zhao, Yi Jin & Jia Zheng

Authors
  1. Zhen Wang
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  2. Xiao Chen
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  3. Yongqiang Zhao
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  4. Yi Jin
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  5. Jia Zheng
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Correspondence to Jia Zheng.

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Wang, Z., Chen, X., Zhao, Y. et al. G-protein-coupled estrogen receptor suppresses the migration of osteosarcoma cells via post-translational regulation of Snail. J Cancer Res Clin Oncol 145, 87–96 (2019). https://doi.org/10.1007/s00432-018-2768-4

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  • DOI: https://doi.org/10.1007/s00432-018-2768-4

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