S1PR3 inhibition impairs cell cycle checkpoint via the AKT/WEE1 pathway in oral squamous cell carcinoma

作者：Xin Zhou, Jinghao Liu, Chen Xu, Xinyu Zhou, Beihui Xu, Guifang Gan, Fuxiang Chen · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06582-4 · 被引用次数：4 · 研究领域：Sphingolipid Metabolism and Signaling、Flavonoids in Medical Research、Caveolin-1 and cellular processes

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 O...