1. G-Protein-coupled Estrogen Receptor 1 Agonist G-1 Perturbs Sunitinib Resistance-related Phosphoproteomic Signatures in Renal Cell Carcinoma.
- Author
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Chen SK, Wang YC, Lin TY, Wu HJ, Huang CJ, and Ku WC
- Subjects
- Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell metabolism, Carcinoma, Renal Cell pathology, Cell Movement drug effects, Cell Proliferation drug effects, Cyclopentanes administration & dosage, Drug Resistance, Neoplasm, Drug Synergism, Humans, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Kidney Neoplasms pathology, Phosphoproteins metabolism, Quinolines administration & dosage, Receptors, Estrogen metabolism, Receptors, G-Protein-Coupled metabolism, Signal Transduction, Sunitinib administration & dosage, Antineoplastic Combined Chemotherapy Protocols pharmacology, Carcinoma, Renal Cell drug therapy, Cyclopentanes pharmacology, Kidney Neoplasms drug therapy, Quinolines pharmacology, Receptors, G-Protein-Coupled agonists, Sunitinib pharmacology
- Abstract
Background: Metastatic renal cell carcinoma (RCC) often develops resistance to first-line targeted therapy such as sunitinib. G-Protein-coupled estrogen receptor 1 (GPER1) agonist G-1 was recently reported to regulate RCC physiology but the role of G-1 in RCC tumorigenesis and sunitinib resistance remains largely unknown., Materials and Methods: Parental and sunitinib-resistant 786-O cells were treated with GPER1 agonist G-1, and quantitative phosphoproteomics was performed. Bioinformatic analyses and validations, including immunoblotting, cell migration, and cell cycle distribution, were performed., Results: G-1 repressed cell proliferation and migration in both parental and sunitinib-resistant 786-O cells. Phosphoproteomic signatures, including phosphoinositide 3-kinase and protein kinase B (PI3K-AKT) as well as other pathways, were up-regulated in sunitinib-resistant cells but application of G-1 reversed this effect. Among phosphoprotein candidates, activating transcription factor 2 (ATF2) Thr69/71 phosphorylation was antagonistically regulated by sunitinib resistance and G-1., Conclusion: Our results open up the possibility for managing RCC and sunitinib resistance by GPER1 agonist G-1 and its regulated pathways., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2021
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