Dual functions of NME1 in suppression of cell motility and enhancement of genomic stability in melanoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-07-15

AUTHORS

David M. Kaetzel, Mary K. Leonard, Gemma S. Cook, Marian Novak, Stuart G. Jarrett, Xiuwei Yang, Alexey M. Belkin

ABSTRACT

The NME1 gene represents the prototypical metastasis suppressor, whose expression inhibits cell motility and metastasis without impact on primary tumor growth in a number of different human cancers. This report outlines our recent efforts to define the molecular mechanisms through which NME1 both suppresses cell motility and promotes genomic integrity in the setting of human melanoma. Forced NME1 expression in a variety of melanoma-derived cell lines was shown to induce dynamic changes in cell morphology and reorganization of the actin cytoskeleton, with formation of a network of thick stress fibers and assembly of fibronectin fibrils at large focal adhesions. Moreover, NME1 expression results in adhesion reprogramming through an impact on integrin repertoire and focal adhesion dynamics. Having previously demonstrated that NME1 expression promotes repair of DNA damage induced by ultraviolet radiation (UVR) in both yeast and mammalian cells, probably via the nucleotide excision repair pathway, we have more recently demonstrated that NME1 is rapidly recruited to double-strand breaks. This preliminary result represents the first evidence of direct interactions between NME1 and DNA in the context of DNA repair and has set the stage for current efforts to probe its functional interactions with double-strand break repair pathways. Discussed herein are molecular models to explain the interactions of NME1 with such diverse cellular functions as cell motility and DNA repair, potentially through its nucleoside diphosphate kinase and 3′-5′ exonuclease activities. More... »

PAGES

199-206

References to SciGraph publications

  • 2000-06. Nm23/Nucleoside Diphosphate Kinase in Human Cancers in JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
  • 2006-05. ARF proteins: roles in membrane traffic and beyond in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2011-06-29. Protein–protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1 in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 2003-03. In vivo cross-linking of nm23/nucleoside diphosphate kinase to the PDGF-A gene promoter in MOLECULAR BIOLOGY REPORTS
  • 2012-06-15. NM23 deficiency promotes metastasis in a UV radiation-induced mouse model of human melanoma in CLINICAL & EXPERIMENTAL METASTASIS
  • 2007-05-07. Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair in NATURE CELL BIOLOGY
  • 2002-05. The 3′–5′ exonucleases in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2003-02. Inhibition of signal transduction by the nm23 metastasis suppressor: Possible mechanisms in CLINICAL & EXPERIMENTAL METASTASIS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00210-014-1010-4

    DOI

    http://dx.doi.org/10.1007/s00210-014-1010-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004275284

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25017017


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