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Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma

Oncogene volume 25, pages 1008–1017 (2006)Cite this article

Abstract

Hepatitis B virus (HBV)-encoded X antigen (HBxAg) contributes to the development of hepatocellular carcinoma (HCC). A frequent characteristic of HCC is reduced or absent expression of the cell adhesion protein, E-cadherin, although it is not known whether HBxAg plays a role. To address this, the levels of E-cadherin were determined in HBxAg-positive and -negative HepG2 cells in culture, and in tumor and surrounding nontumor liver from a panel of HBV carriers. The results showed an inverse relationship between HBxAg and E-cadherin expression both in tissue culture and in vivo. In HBxAg-positive cells, E-cadherin was suppressed at both the mRNA and protein levels. This was associated with hypermethylation of the E-cadherin promoter. Depressed E-cadherin correlated with HBxAg trans-activation function, as did the migration of HepG2 cells in vitro. Decreased expression of E-cadherin was also associated with the accumulation of β-catenin in the cytoplasm and/or nuclei in tissues and cell lines, which is characteristic of activated β-catenin. Additional work showed that HBxAg-activated β-catenin. Together, these results suggest that the HBxAg is associated with decreased expression of E-cadherin, accumulation of β-catenin in the cytoplasm and nucleus, and increased cell migration, which may contribute importantly to hepatocarcinogenesis.

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Acknowledgements

This work was supported by NIH Grants CA48656 and CA66971 to MAF.

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Author notes

  1. J Liu and Z Lian: Drs Liu and Lian contributed equally to this study.

Authors and Affiliations

  1. Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA

    J Liu, Z Lian & M A Feitelson

  2. Department of Digestive Diseases, State Key Laboratory for Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People's Republic of China

    J Liu, S Han, K Wu, J Ding & D Fan

  3. Department of Biochemistry, Chinese University of Hong Kong, Shatin, Hong Kong

    M M Y Waye

  4. Shanghai Eastern Hospital and Institute of Hepatobiliary Surgery, Second Military Medical University, Shanghai, People's Republic of China

    H Wang & M-C Wu

  5. Department of Medicine, Molecular Hepatology Research Unit, University of the Witwatersrand, Johannesburg, South Africa

    P Arbuthnot & M Kew

  6. Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    M A Feitelson

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  1. J Liu
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  2. Z Lian
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Correspondence to M A Feitelson.

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Liu, J., Lian, Z., Han, S. et al. Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma. Oncogene 25, 1008–1017 (2006). https://doi.org/10.1038/sj.onc.1209138

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