TGF ‐β1 Up‐Regulates PLAU Expression to Promote Invasion and Migration of Oral Squamous Cell Carcinoma

ABSTRACT Introduction Dysregulated expression of urokinase‐type plasminogen activator (PLAU), a serine protease, is frequently associated with various cancers. However, in oral squamous cell carcinoma (OSCC), the specific biological functions and mechanisms of action of PLAU remain unclear. Methods Western blot (WB) analysis and quantitative real time polymerase chain reaction experiments verified the protein and mRNA expression of PLAU in oral squamous cell carcinoma; Flow cytometry was used to assess changes in OSCC cell cycle and apoptosis following PLAU knockdown. Transwell assays were conducted to evaluate alterations in cell invasion and migration after PLAU knockdown. LinkedOmics database was employed to analyze the correlation between PLAU and TGF‐β1. Results Our study using GEPIA2 dataset analysis and WB experiments revealed that PLAU expression was upregulated in HNSC tissues and OSCC cell lines and was significantly associated with overall survival in patients. Furthermore, the invasive and migratory abilities of UM1 cells were significantly reduced following PLAU knockdown, as demonstrated by scratch assays and Transwell migration assays. Subsequently, Western blot analysis revealed that PLAU knockdown effectively inhibited the epithelial‐mesenchymal transition (EMT) process. Meanwhile, LinkedOmics database analysis revealed a significant positive correlation between TGF‐β1 and PLAU. Further investigations demonstrated that TGF‐β1 induces PLAU upregulation, which subsequently promotes the migration, invasion, and EMT process in OSCC cells. Conversely, PLAU knockdown abrogates these TGF‐β1‐mediated effects. Conclusion PLAU acts as a key oncogenic driver in OSCC and may serve as a potential diagnostic and prognostic biomarker. More importantly, the TGF‐β1‐PLAU axis may offer new therapeutic targets for OSCC treatment.