Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis

被引：127

作者：

D'Angelo, A

Garzia, L

André, A

Carotenuto, P

Aglio, V

Guardiola, O

Arrigoni, G

Cossu, A

Palmieri, G

Aravind, L

Zollo, M

机构：

[1] Telethon Inst Genet & Med, I-80131 Naples, Italy

[2] Univ Milan, Osped San Raffaele, HSR, Dept Anat & Pathol, I-20127 Milan, Italy

[3] Univ Sassari, Dept Pathol, Azienda ASL 1, I-07100 Sassari, Italy

[4] Consiglio Nazl Ric Tramariglio, Sez Sassari, Ist Chim Biomol, Alghero, Italy

[5] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA

来源：

CANCER CELL | 2004年 / 5卷 / 02期

关键词：

D O I：

10.1016/S1535-6108(04)00021-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：137 / 149

页数：13

共 40 条

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