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Epstein-Barr virus nuclear protein EBNA-3C interacts with the human metastatic suppressor Nm23-H1: A molecular link to cancer metastasis

Nature Medicine volume 7, pages 350–355 (2001)Cite this article

Abstract

Epstein-Barr virus (EBV) is an oncogenic virus associated with a number of human malignancies including Burkitt lymphoma, nasopharyngeal carcinoma, lymphoproliferative disease and, though still debated, breast carcinoma. A subset of latent EBV antigens is required for mediating immortalization of primary B-lymphocytes. Here we demonstrate that the carboxy-terminal region of the essential latent antigen, EBNA-3C, interacts specifically with the human metastatic suppressor protein Nm23-H1. Moreover, EBNA-3C reverses the ability of Nm23-H1 to suppress the migration of Burkitt lymphoma cells and breast carcinoma cells. We propose that EBNA-3C contributes to EBV-associated human cancers by targeting and altering the role of the metastasis suppressor Nm23-H1.

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Figure 1: Structural motifs of Nm23-HI and EBNA-3C.
Figure 2: Epstein-Barr virus nuclear protein EBNA-3C associates with NM23-H1 in vitro.
Figure 3: Nm23-H1 and EBNA-3C interact in human 293 cells in vivo.
Figure 4: Nm23-H1 co-immunoprecipitates with EBNA-3C in stably transfected EBNA-3C expressing cell lines and in EBV-transformed lymphoblastoid cell lines.
Figure 5: Immunofluorescence analysis to determine the cellular localization of Nm23-H1 and EBNA-3C.
Figure 6: Motility of MDA-MB-435 breast carcinoma and BJAB cell lines in the presence of different chemoattractants.

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Acknowledgements

We thank E. Kieff for the EBNA-3C reagents; V. Deretic and J. Poschet for their support and their use of his fluorescence microscopy system; E. Fearon for the MDA-MB-435 cell line; P.S. Steeg and M.T. Hartstough for the pET3C-NM23H1 and pCMV-NM23-H1 constructs; and E. Postel for the NM23-H2 construct. This work was supported by grants from the Leukemia and Lymphoma Society of America and the National Cancer Institute CA072150-01 (to E.S.R.).

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  1. Department of Microbiology and Immunology and the Comprehensive Cancer and Geriatrics Center, Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Chitra Subramanian, Murray A. Cotter II & Erle S. Robertson

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Correspondence to Erle S. Robertson.

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Subramanian, C., Cotter, M. & Robertson, E. Epstein-Barr virus nuclear protein EBNA-3C interacts with the human metastatic suppressor Nm23-H1: A molecular link to cancer metastasis. Nat Med 7, 350–355 (2001). https://doi.org/10.1038/85499

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