Abstract 4210: CPAP contributes to HBx-mediated NF-κB activation in hepatocellular carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC) is a type of tumor that results from chronic inflammation triggered by hepatotropic viruses or other toxic chemicals. Constitutive activation of nuclear factor (NF)-κB is an important event involved in chronic inflammation of the liver. The HBV X protein (HBx) is shown to activate NF-κB by inducing phosphorylation of IκBα and decreasing IκBα stability. Centrosomal protein P4.1-associated protein (CPAP), which plays important roles in centrosomal functions, is previously identified as the transcriptional co-activator of NF-κB. Herein, we demonstrate that CPAP can directly interact with HBx to enhance HBx-mediated NF-κB activation. Knockdown expression of CPAP abolishes this effect, indicating that CPAP is required for HBx-mediated NF-κB activation. In addition, HBx cooperates with cyclic adenosine monophosphate response element-binding protein (CREB) to increase the expression of CPAP by up-regulating its promoter activity. Furthermore, overexpression of CPAP enhances the protein stability of HBx. These results suggest that a positive feedback regulation exists between CPAP and HBx. The stable expression of CPAP in HCC cell lines increases cell proliferation. In addition, the co-expression of CPAP and HBx more greatly enhances the cell proliferation ability than either CPAP or HBx alone. Taken together, our study indicates that CPAP can cooperate with HBx and is important for HBx-induced NF-κB activation. Citation Format: Liang-Yi Hung. CPAP contributes to HBx-mediated NF-κB activation in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4210. doi:10.1158/1538-7445.AM2014-4210