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Title: The Hepatitis B Virus Pre-Core Protein p22 Activates Wnt Signaling.
Austin Authors: Tran, Bang Manh;Flanagan, Dustin James;Ebert, Gregor;Warner, Nadia;Tran, Hoanh;Fifis, Theodora;Kastrappis, Georgios;Christophi, Christopher ;Pellegrini, Marc;Torresi, Joseph ;Phesse, Toby James;Vincan, Elizabeth
Affiliation: Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK
School of Pharmacy and Biomedical Sciences, Curtin University, Perth, WA 6102, Australia
European Cancer Stem Cell Research Institute, Cardiff University, Cardiff CF24 4HQ, UK
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne 3000, Australia
The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Australia
Department of Medical Biology, The University of Melbourne, Melbourne 3010, Australia
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne 3000, Australia
Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne 3000, Australia
Issue Date: 31-May-2020 2020-05-31
Publication information: Cancers 2020; 12(6): E1435
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.
DOI: 10.3390/cancers12061435
ORCID: 0000-0002-4252-086X
PubMed URL: 32486480
ISSN: 2072-6694
Type: Journal Article
Subjects: HBV
Wnt signaling
hepatitis B virus
liver cancer
Appears in Collections:Journal articles

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