This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02222-06v1 81/4/1554    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kondo, S. Articles by Pagano, J. S. Search for Related Content PubMed PubMed Citation Articles by Kondo, S. Articles by Pagano, J. S.

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

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.

Published ahead of print on 6 December 2006.