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, L., Di Dato, V., Scoppettuolo, M.n., Cimmino, F., Correale, S., Pirone, L., Monti, S.m., Bruder, E., Zenko, B., Slavkov, I., Pastorino, F., Ponzoni, M., Schulte, J.h., Schramm, A., et al.. - 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
