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The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner

Oncogene volume 20, pages 3323–3331 (2001)Cite this article

Abstract

Chronic hepatitis B virus infection is strongly associated with the development of hepatocellular carcinoma (HCC). Epithelial tumors are frequently characterized by loss of cadherin expression or function. Cadherin-dependent adhesion prevents the acquisition of a migratory and invasive phenotype, and loss of its function is itself enough for the progression from adenoma to carcinoma. The HBx protein of hepatitis B virus is thought to contribute to the development of the carcinoma, however, its role in the oncogenic and metastatic processes is far from being fully understood. We report herein the ability of HBx to disrupt intercellular adhesion in three different cell lines stably transfected with an inducible HBx expression vector. The linkage between the actin cytoskeleton and cadherin complex, which is essential for its function, is disrupted in the presence of HBx, as indicated by detergent solubility and immunoprecipitation experiments. In addition, β-catenin was tyrosine phosphorylated in HBx-expressing cells. Inhibition of the src family of tyrosine kinases resulted in the prevention of the disruption of adherens junctions. These results suggest that HBx is able to disrupt intercellular adhesion in a src-dependent manner, and provide a novel mechanism by which HBx may contribute to the development of HCC.

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References

  • Balsamo J, Leung T, Ernst H, Zanin MKB, Hoffman S, Lilien J . 1996 J. Cell. Biol. 134: 801–813

  • Baptista M, Kramvis A, Kew MC . 1999 Hepatology 29: 946–953

  • Behrens J, Vakaet L, Friis R, Winterhager E, Roy FV, Mareel MM, Birchmaier W . 1993 J. Cell. Biol. 120: 757–766

  • Chisari FV . 2000 Am. J. Pathol. 156: 1118–1132

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

  • Feitelson MA, Duan L-X . 1997 Am. J. Pathol. 150: 1141–1157

  • Geiger B, Ayalon O . 1992 Annu. Rev. Cell. Biol. 8: 307–332

  • Gottlob K, Fulco M, Levrero M, Graessmann A . 1998a J. Biol. Chem. 273: 33347–33353

  • Gottlob K, Pagano S, Levrero M, Graessmann A . 1998b Cancer Res. 58: 3566–3570

  • Gumbiner BM . 1996 Cell 84: 345–357

  • Haviv I, Shamay M, Doitsh G, Shaul Y . 1998 Mol. Cell. Biol. 18: 1562–1569

  • Hazan RB, Norton L . 1998 J. Biol. Chem. 273: 9078–9084

  • Kekulé A, Lauer U, Weiss L, Luber B, Hofsschneider P . 1993 Nature 361: 742–745

  • Kim CM, Koike K, Saito I, Miyamura T, Jay G . 1991 Nature 351: 317–320

  • Klein NP, Schneider RJ . 1997 Mol. Cell. Biol. 17: 6427–6436

  • Koike K, Moriya K, Yotsuyanagi H, Lino S, Kurokawa K . 1994 J. Clin. Invest. 94: 44–49

  • Kozyraki R, Scoazec JY, Flejou JF, D'Errico A, Bedossa P, Terris B, Fiorentino M, Bringuier AF, Grigioni WF, Feldmann G . 1996 Gastroenterology 110: 1137–1149

  • de La Coste A, Romagnolo B, Billuart P, Renard C-A, Buendia M-A, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A, Perret C . 1998 Proc. Natl. Acad. Sci. USA 95: 8847–8851

  • Lara-Pezzi E, Armesilla AL, Majano PL, Redondo JM, López-Cabrera M . 1998 EMBO J. 17: 7066–7077

  • Lara-Pezzi E, Majano PL, Yáñez-Mó M, Gómez-Gonzalo M, Carretero M, Moreno-Otero R, Sánchez-Madrid F, López-Cabrera M . 2001a J. Hepatol. 34: 409–415

  • Lara-Pezzi E, Serrador JM, Montoya MC, Zamora D, Yáñez-Mó M, Carretero M, Furthmayr H, Sánchez-Madrid F, López-Cabrera M . 2001b Hepatology in press

  • Lee TH, Elledge SJ, Butel JS . 1995 J. Virol. 69: 1107–1114

  • Ludueña MA, Iverson GM, Sussman HH . 1976 J. Cell. Physiol. 91: 119–130

  • Maguire HF, Hoeffler JP, Siddiqui A . 1991 Science 252: 842–844

  • Masaki T, Okada M, Shiratori Y, Rengifo W, Matsumoto K, Maeda S, Kato N, Kanai F, Komatsu Y, Nishioka M, Omata M . 1998 Hepatology 27: 1257–1264

  • Müller T, Choidas A, Reichmann E, UIlrich A . 1999 J. Biol. Chem. 274: 10173–10183

  • Nhieu JT, Renard C-A, Wei Y, Cherqui D, Zafrani ES, Buendia M-A . 1999 Am. J. Pathol. 155: 703–710

  • Perl A-K, Wilgenbus P, Dahl U, Semb H, Christofori G . 1998 Nature 392: 190–193

  • Poussin K, Dienes H, Sirma H, Urban S, Beaugrand M, Franco D, Schirmacher P, Bréchot C, Paterlini-Bréchot P . 1999 Int. J. Cancer 80: 497–505

  • Provost E, Rimmö DL . 1999 Curr. Opin. Cell. Biol. 11: 567–572

  • Roche S, Koegl M, Barone MV, Roussel MF, Courtnidge SA . 1995 Mol. Cell. Biol. 15: 1102–1109

  • Schafer DF, Sorrell MF . 1999 Lancet 353: 1253–1257

  • Sirma H, Giannini C, Poussin K, Paterlini P, Kremsdorf D, Bréchot C . 1999 Oncogene 18: 4848–4859

  • Slagle BL, Lee TH, Medina D, Finegold MJ, Butel JS . 1996 Mol. Carcinog 15: 261–269

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

  • Tarn C, Bilodeau ML, Hullinger RL, Andrisani OM . 1999 J. Biol. Chem. 274: 2327–2338

  • Terradillos O, Billet O, Renard C-A, Levy R, Molina T, Briand P, Buendia MA . 1997 Oncogene 14: 395–404

  • Tlsty TD . 1998 Curr. Opin. Cell. Biol. 10: 647–653

  • Tsukita S, Tsukita S, Nagafuchi A, Yonemura S . 1992 Curr. Opin. Cell. Biol. 4: 834–839

  • Ueda H, UIlrich SJ, Gangemi JD, Kappel CA, Ngo L, Feitelson MA, Jay G . 1995 Nat. Genet. 9: 41–47

  • Vleminckx K, Vakaet L, Mareel M, Fiers W, Roy FV . 1991 Cell 66: 107–119

  • Yu D-Y, Moon H-B, Son J-K, Jeong S, Yu S-L, Yoon H, Han Y-M, Lee C-S, Park J-S, Lee C-H, Hyun B-H, Murakami S, Lee K-K . 1999 J. Hepatol. 31: 123–132

  • Zondervan PE, Wink J, Alers JC, IJzermans JN, Schalm SW, de Man RA, van Dekken H . 2000 J. Pathol. 192: 207–215

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Acknowledgements

This work was supported by grants FIS 00/0602 from Ministerio de Sanidad y Consumo (to M López-Cabrera) and SAF 99/0034-C01 from Plan Nacional de Salud and 2FD97-0680-C02-02 from Ministerio de Educación y Cultura (to F Sánchez-Madrid). E Lara-Pezzi was supported by a fellowship from the Comunidad Autónoma de Madrid.

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Authors and Affiliations

  1. Unidad de Biología Molecular and Servicio de Inmunología, Hospital Universitario de la Princesa, Diego de León, 62, Madrid, 28006, Spain

    Enrique Lara-Pezzi, Francisco Sánchez-Madrid & Manuel López-Cabrera

  2. Centre de Recherche de Biochemie Macromoleculaire, CNRS UPR 1086, Montpellier, cedex 5, 34293, France

    Serge Roche

  3. Department of Basic Medical Sciences, Purdue University, West Lafayette, 47907, Indiana IN, USA

    Ourania M Andrisani

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  1. Enrique Lara-Pezzi
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Lara-Pezzi, E., Roche, S., Andrisani, O. et al. The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner. Oncogene 20, 3323–3331 (2001). https://doi.org/10.1038/sj.onc.1204451

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