This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kondo, S.
Right arrow Articles by Pagano, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kondo, S.
Right arrow Articles by Pagano, J. S.

 Previous Article  |  Next Article 

Journal of Virology, February 2007, p. 1554-1562, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.02222-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

MUC1 Induced by Epstein-Barr Virus Latent Membrane Protein 1 Causes Dissociation of the Cell-Matrix Interaction and Cellular Invasiveness via STAT Signaling{triangledown}

Satoru Kondo,1,4 Tomokazu Yoshizaki,4 Naohiro Wakisaka,4 Toshiyuki Horikawa,1,4 Shigeyuki Murono,4 Kyung Lib Jang,1,5 Irene Joab,6 Mitsuru Furukawa,4 and Joseph S. Pagano1,2,3*

Lineberger Comprehensive Cancer Center,1 Departments of Medicine,2 Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599,3 Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan,4 Department of Microbiology, College of Natural Sciences, Pusan National University, Busan, Korea,5 INSERM U716 Cibles Moléculaires en Cancérologie, IFR Saint Louis, Paris, France6

Received 10 October 2006/ Accepted 27 November 2006

Disruption of cellular adhesion is an essential pathobiologic step leading to tumor dissemination. Mucin 1 (MUC1) is a mucinous glycoprotein expressed at the surfaces of epithelial cells in many tissues and their carcinomas. MUC1 plays crucial roles in tumor invasion and metastasis, especially in opposing cell adhesion. We have shown that virus infection, specifically by the human tumor virus Epstein-Barr virus (EBV) induces a spectrum of cellular invasiveness and metastasis factors. Here we show that expression of MUC1 is increased in diverse latently EBV-infected cell lines that express latent membrane protein 1 (LMP1), the main viral oncoprotein, and that the level of MUC1 was suppressed by expression of a dominant-negative mutant of LMP1. Expression of LMP1 in EBV-negative nasopharyngeal cell lines induces expression of MUC1 through activation of the MUC1 promoter via binding of STAT1 and STAT3. Finally, LMP1 reduces cell adhesion ability, which is restored by inhibition of MUC1 expression with MUC1 small interfering RNA (siRNA). In addition, LMP1 increases cell invasiveness, which is suppressed by MUC1 siRNA. Thus, LMP1 induces MUC1, a factor important in an early step of detachment and release of tumor cells, which along with induction of other invasiveness and angiogenic factors may combine to act in a complex sequential process that culminates in metastasis of EBV-infected tumor cells.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-1183. Fax: (919) 966-9673. E-mail: Joseph_Pagano{at}med.unc.edu.

{triangledown} Published ahead of print on 6 December 2006.

Journal of Virology, February 2007, p. 1554-1562, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.02222-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shair, K. H.Y, Schnegg, C. I., Raab-Traub, N. (2009). Epstein-Barr Virus Latent Membrane Protein-1 Effects on Junctional Plakoglobin and Induction of a Cadherin Switch. Cancer Res. 69: 5734-5742 [Abstract] [Full Text]  
  • Shair, K. H.Y., Schnegg, C. I., Raab-Traub, N. (2008). EBV Latent Membrane Protein 1 Effects on Plakoglobin, Cell Growth, and Migration. Cancer Res. 68: 6997-7005 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»