LPS-induced CXCR4-dependent migratory properties and a mesenchymal-like phenotype of colorectal cancer cells
LPS-induced CXCR4-dependent migratory properties and a mesenchymal-like phenotype of colorectal cancer cells
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LPS诱导的CXCR4依赖性迁移特性和结直肠癌细胞的间质样表型
DOI：
10.1080/19336918.2015.1134404
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发表时间：
2017-01-01
影响因子：
3.2
通讯作者：
Wei, Li-Xin
中科院分区：
文献类型：
--
作者：
Liu, Wen-Ting;Jing, Ying-Ying;Wei, Li-Xin
结直肠癌(CRC)是世界上最常见的癌症，超过50%的患者在病程中会发生肝转移。CXCR4及其配体基质细胞衍生因子1(SDF-1)/趋化因子(C-X-C基序)配体12(CXCL12)是参与多种肿瘤扩散和发展的调节分子。在此，我们发现脂多糖在体内和体外都能促进结肠癌细胞的迁移能力，这与SDF-1/CXCR4轴的激活和上皮-间充质转化(EMT)的发生有关。此外，我们还发现，内毒素通过激活核因子-B信号通路诱导CXCR4的表达和EMT。抑制NF-B途径，恢复上皮表型，减弱CXCR4的表达，抑制细胞的迁移能力。临床上，高水平的CXCR4常与结直肠癌患者的转移和预后不良有关。综上所述，内毒素参与了结直肠癌肝转移的全过程，不仅引起肝损伤，导致SDF-1的产生，而且通过促进CXCR4的表达和EMT的发生，增强了结直肠癌细胞的侵袭潜能，从而促进了细胞的迁移和侵袭。
Colorectal cancer (CRC) is the most commonly diagnosed cancer worldwide, and over 50% of patients will develop hepatic metastasis during the course of their disease. CXCR4 and its ligand, stromal cell-derived factor 1 (SDF-1)/chemokine (C-X-C motif) ligand 12 (CXCL12) have been revealed as regulatory molecules involved in the spreading and progression of a variety of tumors. Here we have shown that lipopolysaccharides (LPS) promoted the migratory capacity of colon cancer cells in vivo and in vitro, which correlated with the activation of SDF-1/CXCR4 axis and epithelial-mesenchymal transition (EMT) occurrence. Additionally, we found that LPS-induced CXCR4 expression and EMT through NF-B signaling pathway activation. And inhibition of NF-B pathway, which recovered the epithelial phenotype and attenuated CXCR4 expression, inhibited cell migratory capacity. Clinically, high levels of CXCR4 always correlated with metastasis and poor prognosis of CRC patients. In conclusion, LPS participate in the whole process of hepatic metastasis of CRC, not only causing liver damage resulting in the production of SDF-1, but also enhancing the invasive potential of CRC cells by promoting CXCR4 expression and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.