Document Detail

Lipopolysaccharide-Induced Toll-Like Receptor 4 Signaling in Cancer Cells Promotes Cell Survival and Proliferation in Hepatocellular Carcinoma.
MedLine Citation:
PMID:  23828139     Owner:  NLM     Status:  Publisher    
BACKGROUND: Recent studies have shown that toll-like receptor 4 (TLR4) is involved in hepatocarcinogenesis. However, the significance of TLR4 signaling in cancer development and progression remains unclear.
AIM: The purpose of this study was to investigate the role of TLR4 in cancer cell survival and proliferation in hepatocellular carcinoma (HCC).
METHODS: Fifty-three HCC and ten normal liver specimens were analyzed by immunohistochemistry, and three cell lines (HL-7702, PLC/PRF/5 and HepG2) were used for in vitro studies. Lipopolysaccharide (LPS), a specific ligand of TLR4, was used to activate TLR4 signaling. The effects of LPS-TLR4 signaling on cell survival, proliferation and invasion were examined. Specific inhibitors of NF-κB and MAPK (JNK, ERK and p38) signaling pathways were used to explore the role of each pathway in LPS-TLR4 signaling.
RESULTS: TLR4 was overexpressed in HCC cell lines and in human HCC tissues, where it correlated with Ki-67 expression. LPS-induced activation of TLR4 signaling promoted cancer cell survival and proliferation. LPS-TLR4 signaling was associated with regulation on the activation of NF-κB and MAPK signaling pathways. LPS-TLR4-induced activation of ERK and JNK signaling promotes cell proliferation through regulating Bax translocation to mitochondria. Activation of NF-κB and p38 mediates cytotoxicity of LPS, and inhibition on these two pathways promotes cell proliferation in HCC cells.
CONCLUSION: Our results indicate that TLR4 signaling in cancer cells promotes cell survival and proliferation in HCC.
Lili Wang; Rong Zhu; Zhiquan Huang; Haigang Li; Hongguang Zhu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-5
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  -     ISSN:  1573-2568     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pathology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, China,
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