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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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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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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DOI: https://doi.org/10.1038/85499
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