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Multiple mechanisms underlie metastasis suppressor function of NM23-H1 in melanoma

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Abstract

nm23-h1 was the first metastasis suppressor gene to be identified in humans, with early studies demonstrating its ability to inhibit the metastatic potential of breast carcinoma and melanoma cell lines. This report outlines recent findings from our laboratory indicating that the metastasis suppressor function of NM23-H1 in human melanoma involves a spectrum of molecular mechanisms. Analysis of NM23-H1-dependent profiles of gene expression in human melanoma cell lines has identified a host of target genes that appear to mediate suppression of directional motility. Of particular interest is a subset of motility-suppressing genes whose regulation by NM23-H1 is independent of its known kinase and 3′–5′ exonuclease activities. In parallel, we have recently observed that NM23-H1 expression appears to be required for genomic stability and for optimal repair of DNA damage produced by ultraviolet radiation and other agents. Thus, NM23-H1 might oppose not only the motile and invasive characteristics of metastatic cells but also the acquisition of mutations that drive malignant progression to the metastatic phenotype itself.

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Authors and Affiliations

  1. Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky, Lexington, KY, 40536-0298, USA

    Marian Novak, Stuart G. Jarrett, Joseph R. McCorkle & David M. Kaetzel

  2. Markey Cancer Center, University of Kentucky, Lexington, KY, 40536-0298, USA

    Marian Novak, Stuart G. Jarrett, Joseph R. McCorkle, Isabel Mellon & David M. Kaetzel

  3. Graduate Center for Toxicology, University of Kentucky, Lexington, KY, 40536-0298, USA

    Isabel Mellon

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  1. Marian Novak
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  2. Stuart G. Jarrett
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Correspondence to David M. Kaetzel.

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Novak, M., Jarrett, S.G., McCorkle, J.R. et al. Multiple mechanisms underlie metastasis suppressor function of NM23-H1 in melanoma. Naunyn-Schmiedeberg's Arch Pharmacol 384, 433–438 (2011). https://doi.org/10.1007/s00210-011-0621-2

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  • DOI: https://doi.org/10.1007/s00210-011-0621-2

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