Exploring the Crosstalk Between RIG-I-mediated Signalling and β-catenin

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and among the leading causes of cancer related death worldwide. Hepatocarcinogenesis has been attributed to chronic viral infection and alterations in signal transduction pathways. This study therefore aimed to explore a putative crosstalk between Sendai virus (SeV)-induced RIG-I-mediated signalling pathway and the Wnt/β-catenin signalling pathway, the latter of which is often misregulated in HCC. HCC-derived Huh7 and RIG-I defective Huh7.5 cell lines were used to elucidate β-catenin and RIG-I-mediated signalling pathways. The results indicate that SeV induced a weak IFN-β response and elicited transcriptional activity of IRF3 but not NF-κB or ATF2/c-Jun. It was also found that SeV elicited β-catenin phosphorylation at S552 with de-layed kinetics in RIG-I independent signalling, and that this appeared to occur via Akt but not Src. However, SeV did not elicit transcriptional activity of β-catenin. Overexpression of RIG-I did not affect β-catenin phosphorylation at S552 or its transcriptional activity, but reconsti-tuted SeV-induced IRF3 phosphorylation in Huh7.5 cells. This study showed a relationship between SeV infection and β-catenin phosphorylation at S552, suggesting a possible crosstalk between both RIG-I-mediated and RIG-I-independent signalling pathways of the innate immune system and a key player of the Wnt signalling pathway – β-catenin. These re-sults may contribute to better understanding of how a chronic virus infection can induce hepatocarcinogenesis by activating the Wnt/β-catenin signalling pathway via the innate im-mune system.