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

Sci Rep. 2013;3:1351. doi: 10.1038/srep01351.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Blotting, Western
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Mutation
  • NM23 Nucleoside Diphosphate Kinases / chemistry
  • NM23 Nucleoside Diphosphate Kinases / genetics
  • NM23 Nucleoside Diphosphate Kinases / metabolism*
  • Neoplasm Metastasis
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Peptides / genetics
  • Peptides / metabolism
  • Phosphoric Monoester Hydrolases
  • Protein Binding
  • Protein Structure, Tertiary
  • Transplantation, Heterologous

Substances

  • Carrier Proteins
  • NM23 Nucleoside Diphosphate Kinases
  • Peptides
  • NME1 protein, human
  • PRUNE1 protein, human
  • Phosphoric Monoester Hydrolases