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

Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5
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DOI:
10.3892/ijmm.2011.656
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发表时间:
2011-07-01
影响因子:
5.4
通讯作者:
Park, Jong-Hwan
Park, Jong-Hwan
中科院分区:
医学3区
文献类型:
--
作者:
Song, Eun-Jung;Kang, Min-Jung;Park, Jong-Hwan

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Toll样受体(TLR)信号转导与肿瘤的发生发展密切相关,包括细胞增殖、血管生成、转移和免疫抑制。在本研究中,我们检测了TLR5在胃癌细胞中的表达及其在细胞增殖中的作用。RT-PCR结果显示,TLR5基因在SNU638、SNU601、SNU216和AGS等胃癌细胞系中均有表达。TLR5激动剂鞭毛素可诱导胃癌细胞产生IL-8和激活核因子-kappaB。此外,鞭毛素可促进所有受检的胃癌细胞的增殖,而脂多糖对SNU638细胞的增殖无影响。用抗体阻断TLR5,恢复鞭毛蛋白促进的SNU638细胞的增殖,表明TLR5对鞭毛蛋白促进的细胞增殖是必不可少的。鞭毛蛋白还可导致SNU638细胞中ERK的磷酸化。ERK抑制剂PD98059恢复了鞭毛蛋白促进的SNU638细胞的增殖能力,提示ERK可能在胃癌细胞的增殖中发挥重要作用。提示TLR5可能通过调节细胞增殖而在胃癌的发生发展中发挥重要作用。
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-kappa B 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.