The Role Of ERK5 Pathway In Cigarette Smoke Induced Epithelial-mesenchymal Transition In Renal Cell Carcinoma Cells

Objectives Abundant evidence shows that cigarette smoke(CS)is a paramount risk factor of renal cell carcinoma(RCC)initiation and development.Epithelial-mesenchymal transition(EMT)is a crucial step in tumorigenesis and also contributes to invasion and metastasis of RCC.The role of ERK5,the lesser studied member of MAPKs family,in regulating CS-induced EMT in RCC cells has not been investigated yet.The aim of this study was to investigate how the ERK5 pathway contributes to cigarette smoke(CS)induced EMT in renal cell carcinoma(RCC)cell lines ACHN and A498.Methods RCC cell lines A498 and ACHN were used as in vitro CS exposure model.The effect of cigarette smoke extract(CSE)treatment on ACHN and A498 was analyzed by western blot,wound healing assay,migration and invasion assay,q RT-PCR,and Immunofluorescence.Specific ERK5 inhibitor,XMD8-92,were used to explore the role of ERK5 in CS-induced EMT in ACHN and A498.Then,western blot,wound healing assay,migration and invasion assay,q RT-PCR,and Immunofluorescence were applied to detect how ERK5 regulates CS-induced EMT in ACHN and A498.Results Exposure of RCC cells to CS induced morphological change,enhanced invasive capacity,reduced epithelial marker expression and increased mesenchymal marker expression.CS-induced biological changes in RCC cells were reversed by ERK5 inhibitor.Conclusion Our findings evidenced that CS promoted ERK5 activation,and that the CS-triggered alteration in the EMT phenotype was reversed by ERK5 inhibition.Inhibition of ERK5 expression may represent an attractive target for advanced renal cell carcinoma therapy.