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Targeting S1PR1 in Thyroid Cancer: Functional Characterization and Proteasome-Mediated Suppression by Quercetin
Hyunjin Moon1, Shiying Li1, Yukyung Hong1
1Laboratory of Signal Transduction, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
Molecular Carcinogenesis
|December 3, 2025
Summary
Sphingosine-1-phosphate receptor 1 (S1PR1) is elevated in thyroid cancer, promoting tumor growth. Quercetin, an anticancer compound, effectively reduces S1PR1 levels, suggesting a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Sphingosine-1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor implicated in various cancers.
- S1PR1's role in thyroid cancer remains largely uninvestigated, despite its general protumorigenic consensus.
Purpose of the Study:
- To investigate the biological activity and role of S1PR1 in thyroid cancer progression.
- To explore potential therapeutic strategies targeting S1PR1 in thyroid cancer.
Main Methods:
- Quantitative analysis of S1PR1 protein levels in thyroid cancer tissues versus normal tissues.
- Cellular localization studies using S1PR1-GFP constructs and sphingosine-1-phosphate stimulation.
- Functional assays (colony formation, migration, invasion) in S1PR1 knockout thyroid cancer cells generated via CRISPR/Cas9.
- Analysis of downstream signaling pathways (STAT3, ERK1/2, AKT) and cell adhesion protein expression.
- Screening of anticancer compounds for their effect on S1PR1 expression, focusing on quercetin.
Main Results:
- S1PR1 protein levels are significantly higher in thyroid cancer tissues compared to adjacent normal tissues.
- S1PR1 exhibits cell membrane localization, with intracellular translocation upon stimulation.
- S1PR1 knockout cells demonstrate significantly reduced colony formation, migration, and invasion.
- Inhibition of STAT3, ERK1/2, and AKT kinase activity and decreased cell adhesion protein expression were observed in S1PR1 knockout cells.
- Quercetin treatment significantly reduced S1PR1 protein levels in thyroid cancer cells.
Conclusions:
- S1PR1 protein expression positively correlates with thyroid cancer progression, similar to other cancer types.
- Targeting S1PR1 may represent a viable therapeutic strategy for thyroid cancer.
- Quercetin shows potential as an anticancer agent for S1PR1-positive thyroid cancer cells.
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