Toll-like receptor 4 signaling promotes epithelial-mesenchymal transition in human hepatocellular carcinoma induced by lipopolysaccharide.
Toll-like receptor 4 signaling promotes epithelial-mesenchymal transition in human hepatocellular carcinoma induced by lipopolysaccharide.
复制标题
DOI：
10.1186/1741-7015-10-98
复制
发表时间：
2012-08-31
期刊：
影响因子：
9.3
通讯作者：
Wei LX
中科院分区：
文献类型：
--
作者：
Jing YY;Han ZP;Sun K;Zhang SS;Hou J;Liu Y;Li R;Gao L;Zhao X;Zhao QD;Wu MC;Wei LX
肝细胞癌（HCC）患者的门静脉和外周静脉中的内毒素水平较高，并且已报道脂多糖（LPS）（革兰氏阴性细菌的细胞壁成分）抑制肿瘤生长。本研究发现LPS诱导的Toll样受体4（TLR 4）信号通路参与了肿瘤的侵袭和生存，并对其分子机制进行了探讨。本研究采用4种肝癌细胞系和裸鼠脾静脉转移模型，研究了LPS诱导的肝癌细胞的侵袭能力和上皮间质转化（EMT）的体内外情况。共106例肝癌患者的临床标本中检测了TLR 4的表达，并分析了其与临床病理特征的关系。体外和体内实验表明，LPS可显著增强肝癌细胞的侵袭能力，并诱导具有TLR 4依赖性的EMT。进一步研究发现，LPS可通过TLR 4直接激活肝癌细胞核因子κ B（NF-κB）信号通路。有趣的是，阻断NF-κB信号传导显著抑制转录因子Snail的表达，从而抑制EMT的发生。肝癌组织中TLR 4的高表达与患者的无癌生存率和总生存率均密切相关。我们的研究结果表明，TLR 4信号是LPS诱导的EMT，肿瘤细胞的侵袭和转移所必需的，这为LPS相关的发病机制提供了分子见解，并为开发新的抗肝癌转移策略提供了基础。
The endotoxin level in the portal and peripheral veins of hepatocellular carcinoma (HCC) patients is higher and lipopolysaccharide (LPS), a cell wall constituent of gram-negative bacteria, has been reported to inhibit tumor growth. However, in this study, we found that LPS-induced toll-like receptor 4 (TLR4) signaling was involved in tumor invasion and survival, and the molecular mechanism was investigated, Four HCC cell lines and a splenic vein metastasis of the nude mouse model were used to study the invasion ability of LPS-induced HCC cells and the epithelia-mesenchymal transition (EMT) in vitro and in vivo. A total of 106 clinical samples from HCC patients were used to evaluate TLR4 expression and analyze its association with clinicopathological characteristics The in vitro and in vivo experiments demonstrated that LPS could significantly enhance the invasive potential and induce EMT in HCC cells with TLR4 dependent. Further studies showed that LPS could directly activate nuclear factor kappa B (NF-κB) signaling through TLR4 in HCC cells. Interestingly, blocking NF-κB signaling significantly inhibited transcription factor Snail expression and thereby inhibited EMT occurrence. High expression of TLR4 in HCC tissues was strongly associated with both poor cancer-free survival and overall survival in patients. Our results indicate that TLR4 signaling is required for LPS-induced EMT, tumor cell invasion and metastasis, which provide molecular insights for LPS-related pathogenesis and a basis for developing new strategies against metastasis in HCC.
登录
查看更多内容
影响因子：
9
作者：
Poon, Ronnie T. P.;Fan, Sheung Tat;Wong, John
通讯作者：
Wong, John
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
DOI：
10.2217/fon.09.91
发表时间：
2009-10
期刊：
Future oncology (London, England)
影响因子：
--
作者：
van Zijl F;Zulehner G;Petz M;Schneller D;Kornauth C;Hau M;Machat G;Grubinger M;Huber H;Mikulits W
通讯作者：
Mikulits W
影响因子：
6.4
作者：
Harmey, JH;Bucana, CD;Dong, ZY
通讯作者：
Dong, ZY
影响因子：
4.8
作者：
Criswell, Tracy L.;Arteaga, Carlos L.
通讯作者：
Arteaga, Carlos L.