Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis.
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.
D'Angelo
Anna
A
Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Naples, Italy.
Garzia
Livia
L
André
Alessandra
A
Carotenuto
Pietro
P
Aglio
Veruska
V
Guardiola
Ombretta
O
Arrigoni
Gianluigi
G
Cossu
Antonio
A
Palmieri
Giuseppe
G
Aravind
L
L
Zollo
Massimo
M
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D004176:Dipyridamole / Q000494:pharmacology; D005090:Exodeoxyribonucleases / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009701:Nucleoside-Diphosphate Kinase; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D002352:Carrier Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D010726:Phosphodiesterase Inhibitors; D011506:Proteins; D004176:Dipyridamole; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D005090:Exodeoxyribonucleases; C070765:recJ protein, Bacteria; C438732:PRUNE1 protein, human; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases