Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5.

Signaling of the Toll-like receptor (TLR) is closely associated with tumor development and progression processes including cell proliferation, angiogenesis, metastasis, and immunosuppression. In this study, we examined the expression of TLR5 in gastric cancer cells and its function in cell proliferation. RT-PCR revealed that the TLR5 gene was expressed in all gastric cancer cell lines examined, SNU638, SNU601, SNU216, and AGS. The TLR5 agonist, flagellin, induced IL-8 production and NF-κB activation in the gastric cancer cell lines. In addition, flagellin enhanced the proliferation of all gastric cancer cells examined, whereas LPS did not affect that of SNU638 cells. Blockade of TLR5 using an antibody, restored the proliferation of SNU638 cells enhanced by flagellin, indicating that TLR5 is essential for cell proliferation by flagellin. Flagellin also led to phosphorylation of ERK in SNU638 cells. The ERK inhibitor, PD98059, restored the proliferation ability of SNU638 cells enhanced by flagellin, suggesting that ERK may play an important role in the proliferation of gastric cancer cells. These findings suggest that TLR5 may play an important role in tumor progression of gastric cancer via the regulation of cell proliferation.