S100A9 promotes prostate cancer cell invasion by activating TLR4/NF-κB/integrin β1/FAK signaling

Background: S100A9, which is expressed in prostate cancer, has been reported in association with prostate cancer progression. However, the role of S100A9 in prostate cancer metastasis is largely unknown. The aim of this study was to investigate the effect of S100A9 on prostate cancer cell invasion and the involved mechanisms. Materials and methods: Integrin beta 1 expression in PC-3 and DU-145 cells was determined by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) and Western blot. Cellular invasion was measured by transwell invasion assay. Western blot was used to determine protein expression. Concentrations of S100A9 and fibronectin were analyzed by enzyme-linked immunosorbent assay. The protein interaction was detected by immunoprecipitation. The NF-kappa B activity was measured by luciferase reporter assay. The DU-145 cells metastasis in vivo was determined in mice xenograft models after S100A9 overexpression. Results: S100A9 promoted prostate cancer cells invasion, integrin beta 1 expression and fibronectin secretion. Further investigation evidenced that S100A9 interacted with Toll-like receptor 4 (TLR4) and activated NF-kappa B, which was responsible for tumor cell invasion, integrin beta 1 up-regulation and focal adhesion kinase (FAK) phosphorylation. Furthermore, integrin beta 1 inhibition led to decreased FAK phosphorylation and reduced tumor cell invasion. Overexpression of S100A9 increased xenograft tumor micro-metastases, integrin beta 1 expression and induced NF-kappa B and FAK activation in vivo. Conclusion: Our study demonstrated that S100A9 promotes prostate cancer cell invasion, and one of the underlying molecular mechanisms is that S100A9 activates integrin beta 1/FAK through TLR4/NF-kappa B signaling leading to metastasis of prostate cancer cell.