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

Marianeve Carotenuto, Emilia Pedone, Donatella Diana, Pasqualino De Antonellis, Sašo Džeroski, Natascia Marino, Luigi Navas, Valeria Di Dato, Maria Nunzia Scoppettuolo, Flora Cimmino, Stefania Correale, Luciano Pirone, Simona Maria Monti, Elisabeth Bruder, Bernard Ženko, Ivica Slavkov, Fabio Pastorino, Mirco Ponzoni, Johannes H. Schulte, Alexander SchrammAngelika Eggert, Frank Westermann, Gianluigi Arrigoni, Benedetta Accordi, Giuseppe Basso, Michele Saviano, Roberto Fattorusso, Massimo Zollo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1351
JournalScientific Reports
Volume3
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • General

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