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Tumor Biology

, Volume 35, Issue 10, pp 10429–10435 | Cite as

LPS promotes epithelial–mesenchymal transition and activation of TLR4/JNK signaling

  • Hangyu Li
  • Yan Li
  • Dan Liu
  • Jingang Liu
Research Article

Abstract

The endotoxin level in the portal and peripheral veins of hepatocellular carcinoma (HCC) patients is higher and lipopolysaccharide (LPS), 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 the molecular mechanism was investigated. The HCC cells were used to study the invasion ability of LPS-induced HCC cells and the epithelial–mesenchymal transition (EMT) in vitro. The in vitro 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 JNK/MAPK signaling through TLR4 in HCC cells. Interestingly, blocking JNK/MAPK signaling significantly inhibited EMT occurrence. Our results indicate that TLR4/JNK/MAPK 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.

Keywords

Toll-like receptor 4 Epithelial–mesenchymal transition Lipopolysaccharide Human hepatocellular carcinoma 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81071955) and the Scientific Research from Educational Department of Liaoning Province, China (No. L2010634)

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of General SurgeryShengjing Hospital Affiliated to China Medical UniversityShenyangChina

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