Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth.
Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth.
复制标题
DOI：
10.1158/0008-5472.can-10-1993
复制
发表时间：
2011-04-01
期刊：
影响因子：
11.2
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Cai Z;Sanchez A;Shi Z;Zhang T;Liu M;Zhang D
越来越多的证据表明，toll样受体（TLRs）是先天免疫的关键受体，在癌症的进展和发展中发挥作用，但不同TLRs的激活可能表现出完全相反的结果，抗肿瘤或促肿瘤作用。TLR在先天免疫细胞中的功能已被广泛研究，因此我们研究了TLR信号在乳腺癌上皮细胞中的作用。我们发现TLR5在乳腺癌中高表达，TLR5信号通路在乳腺癌细胞中反应过度。有趣的是，乳腺癌细胞中的鞭毛蛋白/TLR5信号抑制细胞增殖和非锚定生长，这是致瘤转化的标志。此外，鞭毛蛋白诱导的可溶性因子的分泌以自分泌的方式促进了生长抑制活性。在人乳腺癌细胞的小鼠异种移植物中进一步证实了这种抑制活性。这些发现表明，鞭毛蛋白激活TLR5介导先天免疫反应，从而在乳腺癌细胞中引发强大的抗肿瘤活性，这可能成为人类乳腺癌治疗的新靶点。
Increasing evidence showed that Toll-like receptors (TLRs), key receptors in innate immunity, play a role in cancer progression and development but activation of different TLRs might exhibit the exact opposite outcome, anti-tumor or pro-tumor effects. TLR function has been extensively studied in innate immune cells, so we investigate the role of TLR signaling in breast cancer epithelial cells. We found that TLR5 was highly expressed in breast carcinomas and that TLR5 signaling pathway is overly responsive in breast cancer cells. Interestingly, flagellin/TLR5 signaling in breast cancer cells inhibits cell proliferation and an anchorage-independent growth, a hallmark of tumorigenic transformation. In addition, the secretion of soluble factors induced by flagellin contributed to the growth-inhibitive activity in an autocrine fashion. The inhibitive activity was further confirmed in mouse xenografts of human breast cancer cells. These findings indicate that TLR5 activation by flagellin mediates innate immune response to elicit potent antitumor activity in breast cancer cells themselves, which may serve as a novel therapeutic target for human breast cancer therapy.