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Protein–protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1

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Abstract

Nm23-H1, also known as NDPK-A, was the first of a class of metastasis suppressor genes to be identified. Overexpression of Nm23-H1 in metastatic cell lines (melanoma, breast carcinoma, prostate, colon, hepatocellular, and oral squamous cell carcinoma) reduced cell motility in in vitro assays and metastatic potential in xenograft models, without a significant effect on primary tumor size. The mechanism of Nm23-H1 suppression of metastasis, however, is incompletely understood. Nm23-H1 has been reported to bind proteins, including those in small G-protein complexes, transcriptional complexes, the Map kinase, the TGF-β signaling pathways and the cytoskeleton. Evidence supporting these associations is presented together with evidence of resultant biochemical and phenotypic consequences of association. Cumulatively, the data suggest that part of the anti-metastatic function of Nm23-H1 lies in pathways that it interrupts via binding and inactivation of proteins.

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Acknowledgments

This research was supported by the Intramural program of the National Cancer Institute.

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Authors and Affiliations

  1. Women’s Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA

    Natascia Marino, Jean-Claude Marshall & Patricia S. Steeg

  2. National Institutes of Health, Building 37, Room 1122, Bethesda, MD, 20892, USA

    Natascia Marino & Jean-Claude Marshall

Authors
  1. Natascia Marino
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  2. Jean-Claude Marshall
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  3. Patricia S. Steeg
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Correspondence to Natascia Marino or Jean-Claude Marshall.

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Marino, N., Marshall, JC. & Steeg, P.S. Protein–protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1. Naunyn-Schmiedeberg's Arch Pharmacol 384, 351–362 (2011). https://doi.org/10.1007/s00210-011-0646-6

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  • DOI: https://doi.org/10.1007/s00210-011-0646-6

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