Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with both reduced cell motility in various cancers and increased metastatic potential in neuroblastomas, osteosarcomas, and hematological malignances. We previously reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1. Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells. This series of events suggests that the Nm23-H1/h-Prune protein complex regulates cancer progression and that its specific impairment could be a new therapeutic strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of-concept of our hypothesis, we used a xenograft model of prostate cancer to evaluate whether impairment of this complex using CPP results in an anti-tumoral effect. Using a mouse orthotopic model with bioluminescent imaging, we show evidences that CPP reduces prostate cancer metastases formation. In conclusion, CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise for the treatment of prostate cancer.

A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction / Carotenuto, Marianeve; DE ANTONELLIS, Pasqualino; Chiarolla, Cm; Attanasio, C; Damiani, V; Boffa, I; Aiese, N; Pedone, EMILIA MARIA; Accordi, B; Basso, G; Navas, Luigi; Imbimbo, Ciro; Zollo, Massimo. - In: NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY. - ISSN 0028-1298. - 388:2(2015), pp. 257-269. [10.1007/s00210-014-1035-8]

A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction.

CAROTENUTO, MARIANEVE;DE ANTONELLIS, PASQUALINO;PEDONE, EMILIA MARIA;NAVAS, LUIGI;IMBIMBO, CIRO;ZOLLO, MASSIMO
2015

Abstract

Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with both reduced cell motility in various cancers and increased metastatic potential in neuroblastomas, osteosarcomas, and hematological malignances. We previously reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1. Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells. This series of events suggests that the Nm23-H1/h-Prune protein complex regulates cancer progression and that its specific impairment could be a new therapeutic strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of-concept of our hypothesis, we used a xenograft model of prostate cancer to evaluate whether impairment of this complex using CPP results in an anti-tumoral effect. Using a mouse orthotopic model with bioluminescent imaging, we show evidences that CPP reduces prostate cancer metastases formation. In conclusion, CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise for the treatment of prostate cancer.
2015
A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction / Carotenuto, Marianeve; DE ANTONELLIS, Pasqualino; Chiarolla, Cm; Attanasio, C; Damiani, V; Boffa, I; Aiese, N; Pedone, EMILIA MARIA; Accordi, B; Basso, G; Navas, Luigi; Imbimbo, Ciro; Zollo, Massimo. - In: NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY. - ISSN 0028-1298. - 388:2(2015), pp. 257-269. [10.1007/s00210-014-1035-8]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/585061
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