TLR4 Promotes Breast Cancer Metastasis via Akt/GSK3/-Catenin Pathway upon LPS Stimulation
TLR4 Promotes Breast Cancer Metastasis via Akt/GSK3/-Catenin Pathway upon LPS Stimulation
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DOI：
10.1002/ar.23590
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发表时间：
2017-07-01
影响因子：
2
通讯作者：
Luo, Na
中科院分区：
文献类型：
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作者：
Li, Jun;Yin, Jing;Luo, Na
细菌/病毒诱导的慢性炎症参与肿瘤的发生和进展。Toll样受体4（TLR 4）与多种癌症的发生有关。在这项研究中，我们探讨了脂多糖（LPS）激活TLR 4对乳腺癌转移和相关信号分子的影响。我们首先使用人类乳腺组织微阵列和乳腺细胞系检测了乳腺组织中TLR 4的表达水平。然后，我们使用体外和体内模型研究了LPS刺激TLR 4活化在乳腺癌转移中的作用。最后，我们使用Western印迹和荧光免疫组织化学染色研究了参与该过程的信号分子。结果显示，与正常乳腺组织相比，乳腺癌组织中TLR 4表达水平增加。此外，我们的结果还表明，LPS刺激MCF 7和MDA-MB-231乳腺癌细胞中的TLR 4通路激活引起以下作用：（1）促进乳腺癌细胞的迁移，（2）通过PI 3 K/Akt/GSK 3触发β-连环蛋白信号通路，以及（3）促进导致乳腺癌转移的下游β-连环蛋白靶基因的转录。本研究证实并进一步扩展了LPS激活TLR 4与乳腺癌之间的关系，使用体外和体内模型。这些结果表明Akt/GSK 3/β-catenin信号转导通路可能作为乳腺癌的一个可行的临床治疗靶点。Anat Rec，300：1219-1229，2017。(c)2017年Wiley Periodicals，Inc.
Bacteria/virus-induced chronic inflammation is involved in both tumor initiation and tumor progression. Toll-like receptor 4 (TLR4) has been implicated in the development of several types of cancer. In this study, we explored the impact of TLR4 activation by lipopolysaccharide (LPS) on breast cancer metastasis and associated signaling molecules. We first examined TLR4 expression levels in breast tissue using a human breast tissue microarray and breast cell lines. We then studied the role of TLR4 activation by LPS stimulation in breast cancer metastasis using both in vitro and in vivo models. Finally, we investigated signaling molecules involved in the process using Western blotting and fluorescent immunohistochemistry staining. The results showed that TLR4 expression levels increased in breast cancer tissue compared to normal breast tissue. In addition, our results also showed that TLR4 pathway activation by LPS stimulation in MCF7 and MDA-MB-231 breast cancer cells caused the following actions: (1) promotes migration of breast cancer cells, (2) triggers the -catenin signaling pathway via PI3K/Akt/GSK3, and (3) promotes transcription of downstream -catenin target genes leading to breast cancer metastasis. This study substantiates and further extends the relationship between TLR4 activation by LPS and breast cancer using both in vitro and in vivo models. The results suggest that the Akt/GSK3/-catenin signal transduction pathway may serve as a viable clinical treatment target in breast cancer. Anat Rec, 300:1219-1229, 2017. (c) 2017 Wiley Periodicals, Inc.