Author/Authors :
DʹAngelo، نويسنده , , Anna and Garzia، نويسنده , , Livia and André، نويسنده , , Alessandra and Carotenuto، نويسنده , , Pietro and Aglio، نويسنده , , Veruska and Guardiola، نويسنده , , Ombretta and Arrigoni، نويسنده , , Gianluigi and Cossu، نويسنده , , Antonio and Palmieri، نويسنده , , Giuseppe and Aravind، نويسنده , , L and Zollo، نويسنده , , Massimo، نويسنده ,
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.
