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Understanding h-prune biology in the fight against cancer

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Abstract

The h-prune protein is a member of the DHH protein superfamily, and its overexpression in breast, colorectal and gastric cancers correlates with depth of invasion and degree of lymph-node metastasis. Taken together with the observation that h-prune is highly expressed in metastatic breast cancer, this suggests that h-prune can be used as a marker for the identification of subsets of cancer patients with highly aggressive tumours. H-prune possesses a phosphodiesterase (cAMP-PDE) activity, and inhibition of PDE activity with dipyridamole suppresses cell motility. H-prune interacts with nm23-H1, GSK-3β and gelsolin. Although a correlation between an h-prune PDE activity and cellular motility has been shown, GSK-3β does not affect the PDE activity of h-prune. Inhibition of the interactions between h-prune and GSK-3β and nm23-H1 additively suppresses the migration of colon cancer and breast cancer cells, thus suggesting that h-prune regulates cell motility by two different means of action: through its PDE activity and in its interactions with protein partners. Therefore, the identification of highly specific inhibitors of h-prune should be useful in the development of drugs to treat cancer metastasis.

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Abbreviations

DHH family:

Phosphoesterases with signature motif Asp-His-His

DHHA2:

Asp-His-His family associated motif 2PPase

PDE:

Phosphodiesterase

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

GSK3β:

Glycogen synthase kinase 3 beta

NM23-H1:

Non metastatic protein 23 human

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Acknowledgements

This work was supported by EU BRECOSM-LSH-CT-S03234 grant, EU-FP6 EET-PIPELINE, AIRC and Associazione Italiana per la Lotta al Neuroblastoma, and an AIRC-FIRC Research Fellowship (N.M.). We also thank the CEINGE laboratory and the core activities for several of the strategies developed in the use of proteomic and translational approaches.

We would like to dedicate this review to the memory of a great mentor and supervisor, Graziella Persico, who discovered placenta growth factor-1 and CRIPTO, but who herself died of cancer this year, in 2007.

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  1. CEINGE-Biotecnologie Avanzate SCARL, Via Comunale Margherita 482, 80145, Napoli, Italy

    Natascia Marino & Massimo Zollo

  2. Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via Pansini 5, Naples, Italy

    Massimo Zollo

  3. Facoltà di Scienze Biotecnologiche, Università di Napoli Federico II, Naples, Italy

    Massimo Zollo

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  1. Natascia Marino
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Correspondence to Massimo Zollo.

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Marino, N., Zollo, M. Understanding h-prune biology in the fight against cancer. Clin Exp Metastasis 24, 637–645 (2007). https://doi.org/10.1007/s10585-007-9109-3

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