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

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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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References

  • Bae SH, Jung ES, Park YM, Jang JW, Choi JY, Cho SH et al. (2002). Korean J Hepatol 8: 297–303.

  • Calvisi DF, Ladu S, Conner EA, Factor VM, Thorgeirsson SS . (2004). Lab Invest 84: 1137–1147.

  • Caselmann WH . (1995). J Hepatol 22 (Suppl 1): 34–37.

  • Cha MY, Kim CM, Park YM, Ryu WS . (2004). Hepatology 39: 1683–1693.

  • Christofori G, Semb H . (1999). Trends Biochem Sci 24: 73–76.

  • Endo K, Ueda T, Ueyama J, Ohta T, Terada T . (2000). Human Pathol 31: 558–565.

  • Feitelson MA, Duan LX . (1997). Am J Pathol 150: 1141–1157.

  • Feitelson MA, Reis H, Pan J, Lian Z, Fang J, Liu J et al. (1999) In: Fleig WE (ed). Normal and Malignant Liver Cell Growth: FALK Workshop. Kluwer Academic Publishers: Lancaster, UK. pp 156–170.

    Google Scholar 

  • Feitelson MA, Sun B, Satiroglu Tufan NL, Liu J, Pan J, Lian Z . (2002). Oncogene 21: 2593–2604.

  • Gottardi CJ, Wong E, Gumbiner BM . (2001). J Cell Biol 153: 1049–1060.

  • Henkler F, Koshy R . (1996). J Viral Hepat 3: 109–121.

  • Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB . (1996). Proc Natl Acad Sci USA 93: 9821–9826.

  • Inayoshi J, Ichida T, Sugitani S, Tsuboi Y, Genda T, Honma N et al. (2003). J Gastroenterol Hepatol 18: 673–677.

  • Jiao W, Miyazaki K, Kitajima Y . (2002). Br J Cancer 86: 98–101.

  • Kanai Y, Tsuda H, Sakamoto M, Hirohashi S . (2000). Cancer Lett 148: 73–80.

  • Kanai Y, Ushijima S, Hui AM, Ochiai A, Tsuda H, Sakamoto M et al. (1997). Int J Cancer 71: 355–359.

  • Kondoh N, Wakatsuki T, Hada A, Shuda M, Tanaka K, Arai M et al. (2001). Int J Oncol 18: 1271–1278.

  • Lara-Pezzi E, Majano PL, Yanez-Mo M, Gomez-Gonzalo M, Carretero M, Moreno-Otero R et al. (2001a). J Hepatol 34: 409–415.

  • Lara-Pezzi E, Roche S, Andrisani OM, Sanchez-Madrid F, Lopez-Cabrera M . (2001c). Oncogene 20: 3323–3331.

  • Lara-Pezzi E, Serrador JM, Montoya MC, Zamora D, Yanez-Mo M, Carretero M et al. (2001b). Hepatology 33: 1270–1281.

  • Lee S, Lee HJ, Kim JH, Lee HS, Jang JJ, Kang GH . (2003). Am J Pathol 163: 1371–1378.

  • Lian Z, Liu J, Li L, Li X, Tufan NLS, Clayton MM et al. (2003). Neoplasia 5: 229–244.

  • Lian Z, Pan J, Liu J, Zhang S, Zhu M, Arbuthnot P et al. (1999). Oncogene 18: 1677–1687.

  • Liu J, Feitelson MA . (2004). Methods Mol Med 95: 71–84.

  • Masuda T, Saito H, Kaneko F, Atsukawa K, Morita M, Inagaki H et al. (2000). In vitro Cell Dev Biol 36: 387–394.

  • Matsumura T, Makino R, Mitamura K . (2001). Clin Cancer Res 7: 594–599.

  • Nelson WJ, Nusse R . (2004). Science 303: 1483–1487.

  • Orsulic S, Huber O, Aberle H, Arnold S, Kemler R . (1999). J Cell Sci 112: 1237–1245.

  • Prange W, Breuhahn K, Fischer F, Zilkens C, Pietsch T, Petmecky K et al. (2003). J Pathol 201: 250–259.

  • Slagle BL, Zhou YZ, Birchmeier W, Scorsone KA . (1993). Hepatology 18: 757–762.

  • Su Q, Liu JF, Zhang SX, Li DF, Yang JJ . (1994). Hepatology 19: 788–799.

  • Sun BS, Zhu X, Clayton MM, Pan J, Feitelson MA . (1998). Hepatology 27: 228–239.

  • Terradillos O, Billet O, Renard CA, Levy R, Molina T, Briand P et al. 1997. Oncogene 14: 395–404.

  • Truant R, Antunovic J, Greenblatt J, Prives C, Cromlish JA . (1995). J Virol 69: 1851–1859.

  • Vandeputte DA, Troost D, Leenstra S, Ijlst-Keizers H, Ramkema M, Bosch DA et al. (2002). Glia 38: 329–338.

  • Wang W, London WT, Lega L, Feitelson MA . (1991). Hepatology 14: 29–37.

  • Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC . (1994). Proc Natl Acad Sci USA 91: 2230–2234.

  • Wei Y, Van Nhieu JT, Prigent S, Srivatanakul P, Tiollais P, Buendia MA . (2002). Hepatology 36: 692–701.

  • Wong AST, Gumbiner BM . (2003). J Cell Biol 161: 1191–1203.

  • Wong CM, Fan ST, Ng IO . (2001). Cancer 92: 136–145.

  • Wu JC, Merlino G, Fausto N . (1994). Proc Natl Acad Sci USA 91: 674–678.

  • Yang B, Guo M, Herman JG, Clark DP . (2003). Am J Pathol 163: 1101–1107.

  • Yano T, Hernandez-Blazquez FJ, Omori Y, Yamasaki H . (2001). Carcinogenesis 22: 1593–1600.

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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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  3. S Han
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  4. M M Y Waye
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  6. M-C Wu
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  7. K Wu
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  8. J Ding
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  9. P Arbuthnot
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  10. M Kew
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  11. D Fan
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  12. M A Feitelson
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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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  • DOI: https://doi.org/10.1038/sj.onc.1209138

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