title: LPS promotes epithelial-mesenchymal transition and activation of TLR4/JNK signaling.
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.
authors: Department of General Surgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, Liaoning, China.
authors: Hangyu
authors: H
authors: Li
authors: Yan
authors: Y
authors: Li
authors: Dan
authors: D
authors: Liu
authors: Jingang
authors: J
authors: Liu
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014162:Transfection
chemical_list: D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D048670:MAP Kinase Kinase 4