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

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.


Autore Pugliese

Tutti gli autori

  • Carotenuto M ; Pedone E ; Diana D ; de Antonellis P ; Dzeroski S ; Marino N ; Navas L ; 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 M

Titolo volume/Rivista

Scientific reports


Anno di pubblicazione

2013

ISSN

2045-2322

ISBN

Non Disponibile


Numero di citazioni Wos

Nessuna citazione

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Numero di citazioni Scopus

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Settori ERC

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Codici ASJC

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