Cancers, Vol. 12, Pages 1435: The Hepatitis B Virus Pre-Core Protein p22 Activates Wnt Signaling

Cancers, Vol. 12, Pages 1435: The Hepatitis B Virus Pre-Core Protein p22 Activates Wnt Signaling Cancers doi: 10.3390/cancers12061435 Authors: Bang Manh Tran Dustin James Flanagan Gregor Ebert Nadia Warner Hoanh Tran Theodora Fifis Georgios Kastrappis Christopher Christophi Marc Pellegrini Joseph Torresi Toby James Phesse Elizabeth Vincan 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, ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research