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Updated: Aug 14, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
S1PR3 inhibition impairs cell cycle checkpoint via the AKT/WEE1 pathway in oral squamous cell carcinoma
Xinxia Zhou1, Jinghao Liu1, Xu Chen1
1Department of Clinical Immunology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Background:
Sphingosine-1-phosphate receptor 3 (S1PR3) has been implicated in promoting tumor progression in various cancers. However, the role and molecular mechanisms of S1PR3 in oral squamous cell carcinoma (OSCC) remain poorly understood. The aims of this study were to investigate the function of S1PR3 in OSCC progression and its potential as a therapeutic target.
Method:
The expression of S1PR3 was determined through qPCR, Western blotting analysis, immunohistochemistry (IHC), and the TCGA database. The correlation between S1PR3 expression and clinical prognosis was analyzed using the TCGA database and IHC. The effects of S1PR3 on OSCC cell proliferation and cell cycle were investigated through CCK-8 assay, colony formation assay, EdU incorporation assay, cell cycle analysis, and a xenograft mouse model. The potential mechanisms through which S1PR3 affects the OSCC cell cycle were explored using RNA-seq and a cell cycle array. The effects of combining S1PR3 antagonist with cisplatin on OSCC cell growth were examined through CCK-8 and EdU incorporation assays.
Results:
S1PR3 was overexpressed in OSCC and the upregulation of S1PR3 in OSCC was correlated with unfavorable clinicopathological characteristics and adverse prognosis. Targeting S1PR3 reduced AKT phosphorylation, which led to a downregulation of WEE1, a kinase involved in cell cycle regulation. This downregulation resulted in reducing CDC2 phosphorylation, disrupting the G2/M cell cycle checkpoint and inhibiting OSCC cell proliferation. Furthermore, the combination of S1PR3 antagonist exhibited synergistic inhibitory effects on OSCC cell growth when combined with cisplatin.
Conclusions:
These findings reveal a critical role for S1PR3 in regulating OSCC cell cycle via the AKT/WEE1/CDC2 pathway, thus offering a basis for developing treatment strategies for OSCC patients.
Insights
Sphingosine-1-phosphate receptor 3 (S1PR3) promotes oral cancer growth by disrupting the cell cycle. Targeting S1PR3 inhibits tumor progression and enhances cisplatin effectiveness in oral squamous cell carcinoma (OSCC) treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Sphingosine-1-phosphate receptor 3 (S1PR3) is implicated in various cancers.
- Its specific role and mechanisms in oral squamous cell carcinoma (OSCC) are not well understood.
Purpose of the Study:
- Investigate the function of S1PR3 in OSCC progression.
- Evaluate S1PR3 as a potential therapeutic target for OSCC.
Main Methods:
- Assessed S1PR3 expression using qPCR, Western blotting, IHC, and TCGA data.
- Analyzed S1PR3's impact on OSCC proliferation, cell cycle, and prognosis.
- Explored molecular mechanisms via RNA-seq and cell cycle arrays.
- Tested combination therapy with an S1PR3 antagonist and cisplatin.
Main Results:
- S1PR3 is overexpressed in OSCC, correlating with poor prognosis.
- Targeting S1PR3 reduced AKT/WEE1/CDC2 phosphorylation, inhibiting cell cycle progression.
- S1PR3 inhibition disrupted the G2/M checkpoint and suppressed OSCC proliferation.
- Combined S1PR3 antagonist and cisplatin showed synergistic anti-tumor effects.
Conclusions:
- S1PR3 critically regulates the OSCC cell cycle through the AKT/WEE1/CDC2 pathway.
- S1PR3 represents a promising therapeutic target for OSCC treatment.
- Combination therapy may enhance treatment efficacy for OSCC patients.
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