Shi Ming, Yao Yuanfei, Han Fang, Li Yiqun, Li Yu
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
PLoS One. 2014 Jan 23;9(1):e86839. doi: 10.1371/journal.pone.0086839. eCollection 2014.
Targeting TLR5 signaling in breast cancer represents a novel strategy in cancer immunotherapy. However, the underlying mechanism by which TLR5 signaling inhibits cancer cell proliferation and tumor growth has not been elucidated. In this study, we found TLR5 agonist flagellin inhibited the cell state of activation and induced autophagy, and reported that autophagy protein MAP1S regulated the flagellin/TLR5 signaling pathway in breast cancer cells through enhancement of NF-κB activity and cytokine secretion. Remarkably, MAP1S played a critical role in tumor suppression induced by flagellin, and knockdown of MAP1S almost completely abrogated the suppression of tumor growth and migration by flagellin treatment. In addition, elevated expression of MAP1S in response to flagellin feed-back regulated tumor inflammatory microenvironment in the late stages of TLR5 signaling through degradation of MyD88 in autophagy process. These results indicate a mechanism of antitumor activity that involves MAP1S-controlled TLR5 signaling in breast cancer.
靶向乳腺癌中的TLR5信号通路是癌症免疫治疗中的一种新策略。然而，TLR5信号通路抑制癌细胞增殖和肿瘤生长的潜在机制尚未阐明。在本研究中，我们发现TLR5激动剂鞭毛蛋白抑制激活细胞状态并诱导自噬，并报道自噬蛋白MAP1S通过增强NF-κB活性和细胞因子分泌来调节乳腺癌细胞中的鞭毛蛋白/TLR5信号通路。值得注意的是，MAP1S在鞭毛蛋白诱导的肿瘤抑制中起关键作用，敲低MAP1S几乎完全消除了鞭毛蛋白处理对肿瘤生长和迁移的抑制作用。此外，响应鞭毛蛋白，MAP1S表达升高，通过在自噬过程中降解MyD88，在TLR5信号传导后期反馈调节肿瘤炎性微环境。这些结果表明了一种抗肿瘤活性机制，该机制涉及乳腺癌中MAP1S控制的TLR5信号通路。
