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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites / genetics
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Blotting, Western
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Female
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Gene Expression Regulation, Neoplastic
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HEK293 Cells
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Humans
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Immunohistochemistry
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Magnetic Resonance Spectroscopy
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Mice
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Mice, Nude
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Models, Molecular
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Mutation
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NM23 Nucleoside Diphosphate Kinases / chemistry
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NM23 Nucleoside Diphosphate Kinases / genetics
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NM23 Nucleoside Diphosphate Kinases / metabolism*
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Neoplasm Metastasis
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Neuroblastoma / genetics
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Neuroblastoma / metabolism*
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Neuroblastoma / pathology
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Peptides / genetics
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Peptides / metabolism
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Phosphoric Monoester Hydrolases
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Protein Binding
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Protein Structure, Tertiary
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Transplantation, Heterologous
Substances
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Carrier Proteins
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NM23 Nucleoside Diphosphate Kinases
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Peptides
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NME1 protein, human
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PRUNE1 protein, human
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Phosphoric Monoester Hydrolases