Serum response factor increases renal cell carcinoma migration and invasion through promoting epithelial-mesenchymal transition.

To explore the regulation and function of serum response factor in epithelial-mesenchymal transition in renal cell carcinoma. First, bioinformatics analysis of human renal cell carcinoma tissues was carried out. Then, the expression of serum response factor, mesenchymal markers (N-cadherin, vimentin and fibronectin) and epithelial markers (zonula occludens-1 and epithelial cadherin) was examined in 786-O cells (a human renal cell carcinoma cell line). Serum response factor was overexpressed with pcDNA-serum response factor plasmid, and suppressed by CCG-1423 (a small molecule inhibitor of serum response factor) to study how serum response factor affects epithelial-mesenchymal transition in renal cell carcinoma. A xenograft nude mouse model was established to explore whether serum response factor affected the tumorigenic ability of renal cell carcinoma cells. Serum response factor interacted with several important differentially expressed genes in renal cell carcinoma. In 786-O cells, serum response factor, N-cadherin, vimentin and fibronectin were upregulated, whereas zonula occludens-1 and epithelial cadherin were downregulated. Serum response factor upregulation in 786-O cells increased the Snail expression. Serum response factor suppression reduced Snail induction, and migration and invasion in renal cell carcinoma, which decreased the xenograft tumor volume. Serum response factor is a critical transcription factor in human renal cell carcinoma. Increased serum response factor activity induces epithelial-mesenchymal transition, migration and invasion in 786-O cells, and facilitates the progression of renal cell carcinoma. Targeting serum response factor with CCG-1423 might be an attractive therapeutic strategy for renal cell carcinoma.