Nm23-H1 is one of the most interesting candidate genes for a relevant role in Neuroblastoma pathogenesis. H-Prune is the most characterized Nm23-H1 binding partner, and its overexpression has been shown in different human cancers. Our study focuses on the role of the Nm23-H1/h-Prune protein complex in Neuroblastoma. Using NMR spectroscopy, we performed a conformational analysis of the h-Prune C-terminal to identify the amino acids involved in the interaction with Nm23-H1. We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation. Meta-analysis performed on three Neuroblastoma cohorts showed Nm23-H1 as the gene highly associated to Neuroblastoma aggressiveness. We also identified two other proteins (PTPRA and TRIM22) with expression levels significantly affected by CPP. These data suggest a new avenue for potential clinical application of CPP in Neuroblastoma treatment.

Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction / Carotenuto, M; Pedone, E; Diana, D; de Antonellis, P; Džeroski, S; Marino, N; Navas, Luigi; Di Dato, V; Scoppettuolo, Mn; Cimmino, F; Correale, S; Pirone, L; Monti, Sm; Bruder, E; Zenko, B; Slavkov, I; Pastorino, F; Ponzoni, M; Schulte, Jh; Schramm, A; Eggert, A; Westermann, F; Arrigoni, G; Accordi, B; Basso, G; Saviano, M; Fattorusso, R; Zollo, Massimo. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 3:1351(2013), pp. 1351-1362. [10.1038/ srep01351.]

Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.

Diana D;de Antonellis P;NAVAS, LUIGI;ZOLLO, MASSIMO
2013

Abstract

Nm23-H1 is one of the most interesting candidate genes for a relevant role in Neuroblastoma pathogenesis. H-Prune is the most characterized Nm23-H1 binding partner, and its overexpression has been shown in different human cancers. Our study focuses on the role of the Nm23-H1/h-Prune protein complex in Neuroblastoma. Using NMR spectroscopy, we performed a conformational analysis of the h-Prune C-terminal to identify the amino acids involved in the interaction with Nm23-H1. We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation. Meta-analysis performed on three Neuroblastoma cohorts showed Nm23-H1 as the gene highly associated to Neuroblastoma aggressiveness. We also identified two other proteins (PTPRA and TRIM22) with expression levels significantly affected by CPP. These data suggest a new avenue for potential clinical application of CPP in Neuroblastoma treatment.
2013
Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction / Carotenuto, M; Pedone, E; Diana, D; de Antonellis, P; Džeroski, S; Marino, N; Navas, Luigi; Di Dato, V; Scoppettuolo, Mn; Cimmino, F; Correale, S; Pirone, L; Monti, Sm; Bruder, E; Zenko, B; Slavkov, I; Pastorino, F; Ponzoni, M; Schulte, Jh; Schramm, A; Eggert, A; Westermann, F; Arrigoni, G; Accordi, B; Basso, G; Saviano, M; Fattorusso, R; Zollo, Massimo. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 3:1351(2013), pp. 1351-1362. [10.1038/ srep01351.]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/548696
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