Interaction of PTPRO and TLR4 signaling in hepatocellular carcinoma
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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.
KeywordsProtein tyrosine phosphatase receptor type O Toll-like receptor 4 Hepatocellular carcinoma NF-κB
This work was supported by grants from the National Natural Science Foundation for Distinguished Young Scholars (81225017) and the National Natural Science Foundation (81072029 and 91029721). This work also supported in part by the program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU and the Priority Academic Program of Jiangsu Higher Education Institutions.
Conflict of interest
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