TY - JOUR
T1 - Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction
AU - Carotenuto, Marianeve
AU - Pedone, Emilia
AU - Diana, Donatella
AU - De Antonellis, Pasqualino
AU - Džeroski, Sašo
AU - Marino, Natascia
AU - Navas, Luigi
AU - Di Dato, Valeria
AU - Scoppettuolo, Maria Nunzia
AU - Cimmino, Flora
AU - Correale, Stefania
AU - Pirone, Luciano
AU - Monti, Simona Maria
AU - Bruder, Elisabeth
AU - Ženko, Bernard
AU - Slavkov, Ivica
AU - Pastorino, Fabio
AU - Ponzoni, Mirco
AU - Schulte, Johannes H.
AU - Schramm, Alexander
AU - Eggert, Angelika
AU - Westermann, Frank
AU - Arrigoni, Gianluigi
AU - Accordi, Benedetta
AU - Basso, Giuseppe
AU - Saviano, Michele
AU - Fattorusso, Roberto
AU - Zollo, Massimo
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1038/srep01351
DO - 10.1038/srep01351
M3 - Article
C2 - 23448979
AN - SCOPUS:84875161184
VL - 3
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 1351
ER -