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.
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.
Authors: Robert F Schwabe; Cynthia A Bradham; Tetsuya Uehara; Etsuro Hatano; Brydon L Bennett; Robert Schoonhoven; David A Brenner Journal: Hepatology Date: 2003-04 Impact factor: 17.425
Authors: M Szajnik; M J Szczepanski; M Czystowska; E Elishaev; M Mandapathil; E Nowak-Markwitz; M Spaczynski; T L Whiteside Journal: Oncogene Date: 2009-12-10 Impact factor: 9.867
Authors: Jessica S Citronberg; Lynne R Wilkens; Loic Le Marchand; Unhee Lim; Kristine R Monroe; Meredith A J Hullar; Emily White; Polly A Newcomb; Johanna W Lampe Journal: Cancer Causes Control Date: 2017-11-30 Impact factor: 2.506