title: Interaction of PTPRO and TLR4 signaling in hepatocellular carcinoma.
abstract: Protein tyrosine phosphatase receptor type O (PTPRO) has been identified as a tumor suppressor in a number of cancers including hepatocellular carcinoma (HCC). Toll-like receptor 4 (TLR4) plays diverse roles in HCC tumorigenesis and progression. The association between PTPRO and TLR4 signaling in HCC remains largely unknown. We aimed to clarify the interaction between PTPRO and TLR4 in HCC. Surprisingly, we found reduced and positive-related expression of TLR4 and PTPRO in 84 human HCC specimens. Increased TLR4 expression and activity was found in PTPRO-overexpressed HCC cells stimulated with lipopolysaccharide (LPS). The feedback regulation of PTPRO and TLR4 was dependent on nuclear factor-κB (NF-κB) activation, as suggested by NF-κB inhibition and luciferase reporter assay. Our study suggests that the effect of PTPRO on TLR4 signaling is dependent on NF-κB pathway, suggesting an interesting PTPRO/TLR4/NF-κB signaling feedback loop in HCC carcinogenesis and progression.
authors.affiliation: Department of Rheumatology, the First Affiliated Hospital, Nanjing Medical University, 210029, Nanjing, China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Xu
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.forename: Shushan
authors.initials: S
authors.lastname: Yan
authors.forename: Yin
authors.initials: Y
authors.lastname: Yin
authors.forename: Jiajie
authors.initials: J
authors.lastname: Hou
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.forename: Beicheng
authors.initials: B
authors.lastname: Sun
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014162:Transfection
chemical_list: D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C516888:PTPRO protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3