title: 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.
authors: Centro di Ingegneria Genetica e Biotecnologie Avanzate-CEINGE, Naples, Italy.
authors: Marianeve
authors: M
authors: Carotenuto
authors: Emilia
authors: E
authors: Pedone
authors: Donatella
authors: D
authors: Diana
authors: Pasqualino
authors: P
authors: de Antonellis
authors: Sašo
authors: S
authors: Džeroski
authors: Natascia
authors: N
authors: Marino
authors: Luigi
authors: L
authors: Navas
authors: Valeria
authors: V
authors: Di Dato
authors: Maria Nunzia
authors: MN
authors: Scoppettuolo
authors: Flora
authors: F
authors: Cimmino
authors: Stefania
authors: S
authors: Correale
authors: Luciano
authors: L
authors: Pirone
authors: Simona Maria
authors: SM
authors: Monti
authors: Elisabeth
authors: E
authors: Bruder
authors: Bernard
authors: B
authors: Zenko
authors: Ivica
authors: I
authors: Slavkov
authors: Fabio
authors: F
authors: Pastorino
authors: Mirco
authors: M
authors: Ponzoni
authors: Johannes H
authors: JH
authors: Schulte
authors: Alexander
authors: A
authors: Schramm
authors: Angelika
authors: A
authors: Eggert
authors: Frank
authors: F
authors: Westermann
authors: Gianluigi
authors: G
authors: Arrigoni
authors: Benedetta
authors: B
authors: Accordi
authors: Giuseppe
authors: G
authors: Basso
authors: Michele
authors: M
authors: Saviano
authors: Roberto
authors: R
authors: Fattorusso
authors: Massimo
authors: M
authors: Zollo
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014183:Transplantation, Heterologous
chemical_list: D002352:Carrier Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D010455:Peptides; C517938:NME1 protein, human; C438732:PRUNE1 protein, human; D010744:Phosphoric Monoester Hydrolases