Fig 2: PAI-1 drives EndoMT and aberrant lymphangiogenesis and correlates with poor prognosis in CSCC. A Representative images of CSCC tissues stained for LYVE-1 (green), a-SMA (red), or PAI-1 (purple). Blue indicates the nucleus. B The correlation between PAI-1 expression level and LVD in CSCC tissues. C The correlation between PAI-1 expression level and the percentage of a-SMA.+LVs in CSCC tissues. D and E The OS (D) and DFS (E) of CSCC patients from the TCGA with lower versus higher PAI-1 expression were estimated using Kaplan–Meier curves. The median expression was used as the cut-off value. Data are presented as the mean ± SD. **P < 0.0001

Fig 3: Schematic model. CAF-derived PAI-1 induces EndoMT in tumour-associated LECs by activating the LRP1/ERK1/2/AKT signalling pathway, which in turn drives abnormal lymphangiogenesis by increasing LEC migration, tube formation and monolayer permeability, thereby facilitating tumour lymphoinvasion and CSCC progression

Fig 4: Secreted extracellular PAI-1 promotes EndoMT in LECs by activating the LRP-ERK-AKT signalling pathways. A Western blotting analysis of the signalling pathways activated in PAI-1-treated HDLECs. B HDLECs transduced with siNC or siLRP1 were treated with ECM or CM for 1 h. Cell lysates were analysed by Western blotting. C The migration, tube formation and transendothelial assays were analysed following the indicated treatments. D Western blot analysis of ERK1/2 activation and the expression levels of VE-cadherin, a-SMA, FAP, and vimentin in HDLECs treated or not with PAI-1 in the presence of control or U0126 (ERK1/2 inhibitor) for 1 h. E Western blot analysis of AKT activation and the expression levels of VE-cadherin, a-SMA, FAP, and vimentin in HDLECs treated or not with PAI-1 in the presence of control or MK2206 (AKT inhibitor) for 1 h. F. The migration, tube formation and transendothelial assays were analysed following the treatments described in D. G The migration, tube formation and transendothelial assays were analysed following the treatments described in E Error bars represent the mean ± SD of three independent experiments. *, P < 0.05; **, P < 0.01