Abstract
We identify a new enzymatic activity underlying metastasis in breast cancer and describe its susceptibility to therapeutic inhibition. We show that human prune (h-prune), a phosphoesterase DHH family appertaining protein, has a hitherto unrecognized cyclic nucleotide phosphodiesterase activity effectively suppressed by dipyridamole, a phosphodiesterase inhibitor. h-prune physically interacts with nm23-H1, a metastasis suppressor gene. The h-prune PDE activity, suppressed by dipyridamole and enhanced by the interaction with nm23-H1, stimulates cellular motility and metastasis processes. Out of 59 metastatic breast cancer cases analyzed, 22 (37%) were found to overexpress h-prune, evidence that this novel enzymatic activity is involved in promoting cancer metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Bacterial Proteins / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / physiopathology
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Carrier Proteins / metabolism*
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Cell Movement / physiology
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Dipyridamole / pharmacology
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Exodeoxyribonucleases / genetics
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Gene Expression Regulation / physiology
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Genes, Tumor Suppressor / physiology
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Humans
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Molecular Sequence Data
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Mutation
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NM23 Nucleoside Diphosphate Kinases
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Neoplasm Metastasis / physiopathology
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Nucleoside-Diphosphate Kinase*
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Phosphodiesterase Inhibitors / pharmacology
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Phosphoric Diester Hydrolases / drug effects
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Phosphoric Diester Hydrolases / metabolism
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Phosphoric Monoester Hydrolases
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Protein Structure, Tertiary / physiology
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Proteins / metabolism*
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Sequence Homology, Amino Acid
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Tumor Cells, Cultured
Substances
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Bacterial Proteins
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Carrier Proteins
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NM23 Nucleoside Diphosphate Kinases
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Phosphodiesterase Inhibitors
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Proteins
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Dipyridamole
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NME1 protein, human
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Nucleoside-Diphosphate Kinase
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Exodeoxyribonucleases
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recJ protein, Bacteria
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PRUNE1 protein, human
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Phosphoric Monoester Hydrolases
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Phosphoric Diester Hydrolases