The hepatitis B virus pre-core protein p22 activates Wnt signaling

Tran, B. M. et al. (2020) The hepatitis B virus pre-core protein p22 activates Wnt signaling. Cancers, 12(6), 1435. (doi: 10.3390/cancers12061435) (PMID:32486480) (PMCID:PMC7352296)

Abstract

An emerging theme for Wnt-addicted cancers is that the pathway is regulated at multiple steps via various mechanisms. Infection with hepatitis B virus (HBV) is a major risk factor for liver cancer, as is deregulated Wnt signaling, however, the interaction between these two causes is poorly understood. To investigate this interaction, we screened the effect of the various HBV proteins for their effect on Wnt/β-catenin signaling and identified the pre-core protein p22 as a novel and potent activator of TCF/β-catenin transcription. The effect of p22 on TCF/β-catenin transcription was dose dependent and inhibited by dominant-negative TCF4. HBV p22 activated synthetic and native Wnt target gene promoter reporters, and TCF/β-catenin target gene expression in vivo. Importantly, HBV p22 activated Wnt signaling on its own and in addition to Wnt or β-catenin induced Wnt signaling. Furthermore, HBV p22 elevated TCF/β-catenin transcription above constitutive activation in colon cancer cells due to mutations in downstream genes of the Wnt pathway, namely APC and CTNNB1. Collectively, our data identifies a previously unappreciated role for the HBV pre-core protein p22 in elevating Wnt signaling. Understanding the molecular mechanisms of p22 activity will provide insight into how Wnt signaling is fine-tuned in cancer.

• Item Type: Articles
• Additional Information: This research was funded by Melbourne Health through a project grant number PG-002-2016 awarded to E.V.; T.J.P.; G.E.; N.W.; T.F.; and C.C.; and a post-graduate scholarship to B.M.T.; E.V.; and T.J.P. were funded, in part, by grants from the National Health and Medical Research Council (NHMRC), project grant number APP1099302 and investigator grant number APP1181580. T.J.P. was funded by BLS/CMU Fellowship and MRC (MR/R026424/1). D.J.F.; was funded, in part, by a Cancer Council of Victoria fellowship and a Melbourne Health early career grant GIA-033-2016.
• Keywords: Wnt signaling, hepatitis B virus, HBV, cancer, liver cancer, β-catenin, TCF/LEF.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Flanagan, Dr Dustin

Creator Roles

Flanagan, D. J.: Formal analysis, Funding acquisition, Investigation, Methodology, Visualization, Writing – review and editing

• Authors: Tran, B. M., Flanagan, D. J., Ebert, G., Warner, N., Tran, H., Fifis, T., Kastrappis, G., Christophi, C., Pellegrini, M., Torresi, J., Phesse, T. J., and Vincan, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancers
• Publisher: MDPI
• ISSN: 2072-6694
• ISSN (Online): 2072-6694
• Published Online: 31 May 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Cancers 12(6): 1435
• Publisher Policy: Reproduced under a Creative Commons License