Pai-1 Induced By Chronic Stress Promotes Oral Cancer Metastasis

This study investigates the role of chronic stress in promoting lymphatic metastasis of oral squamous cell carcinoma (OSCC) through the upregulation of plasminogen activator inhibitor-1 (PAI-1). Furthermore, it validates the therapeutic potential of targeting this pathway and advocates for the integration of anti-stress combination therapies. This study investigates the role of PAI-1 in chronic stress-induced epithelial-mesenchymal transition (EMT) of CAL-27 cells, utilizing cortisol and norepinephrine stimulation. Proliferation, migration, and invasion were assessed through CCK-8, scratch, and Transwell assays. The expression levels of PAI-1 and EMT markers (E-cadherin, N-cadherin, and Vimentin) were analyzed using Western blotting and quantitative PCR (q-PCR). The functional necessity of PAI-1 was validated through siRNA-mediated knockdown. Furthermore, immunofluorescence was employed to elucidate the subcellular localization of PAI-1 and the dynamics of EMT-related proteins. Cortisol and norepinephrine upregulated PAI-1 expression in CAL-27 cells, promoting an EMT phenotype characterized by reduced E-cadherin and elevated levels of N-cadherin and Vimentin. This hormonal influence also enhanced cellular proliferation, migration, and invasion. The knockdown of PAI-1 using siRNA effectively reversed the alterations in EMT markers induced by stress and suppressed the associated malignant phenotypes. Furthermore, the expression and subcellular localization of PAI-1 were found to be closely linked to the dynamics of EMT-related proteins. Chronic stress can promote EMT and lymphatic metastasis of OSCC by up-regulating PAI-1.