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

被引：33

作者：

Carotenuto, Marianeve ^{[1
,2
]}

Pedone, Emilia ^{[3
]}

Diana, Donatella ^{[3
]}

de Antonellis, Pasqualino ^{[1
,2
]}

Dzeroski, Saso ^{[7
]}

Marino, Natascia ^{[1
,14
]}

Navas, Luigi ^{[5
]}

Di Dato, Valeria ^{[1
,2
]}

Scoppettuolo, Maria Nunzia ^{[1
,2
]}

Cimmino, Flora ^{[1
,2
]}

Correale, Stefania ^{[3
]}

Pirone, Luciano ^{[13
]}

Monti, Simona Maria ^{[3
]}

Bruder, Elisabeth ^{[6
]}

Zenko, Bernard ^{[7
]}

Slavkov, Ivica ^{[7
]}

Pastorino, Fabio ^{[8
]}

Ponzoni, Mirco ^{[8
]}

Schulte, Johannes H. ^{[9
]}

Schramm, Alexander ^{[9
]}

Eggert, Angelika ^{[9
]}

Westermann, Frank ^{[10
]}

Arrigoni, Gianluigi ^{[11
]}

Accordi, Benedetta

Basso, Giuseppe ^{[12
]}

Saviano, Michele ^{[13
]}

Fattorusso, Roberto ^{[3
,4
]}

Zollo, Massimo ^{[1
,2
]}

机构：

[1] Ctr Ingn Genet & Biotecnol Avanzate CEINGE, Naples, Italy

[2] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy

[3] CNR, Ist Biostrutture & Bioimmagini, I-80125 Naples, Italy

[4] Univ Naples 2, Dipartimento Sci Ambientali, Caserta, Italy

[5] Univ Naples Federico II, Sez Clin Chirurg, Dipartimento Sci Clin Vet, Naples, Italy

[6] Univ Basel, Dept Pathol, Basel, Switzerland

[7] Jozef Stefan Inst, Dept Knowledge Technol, Ljubljana 1000, Slovenia

[8] Osped Pediat, Ist Giannina Gaslini, I-16148 Genoa, Italy

[9] Univ Childrens Hosp Essen, Dept Paediat Oncol & Haematol, D-45122 Essen, Germany

[10] German Canc Res Ctr, Dept Tumour Genet, Heidelberg, Germany

[11] Univ Milan, Osped San Raffaele, Dept Pathol, I-20127 Milan, Italy

[12] Univ Padua, Dept Paediat, Haematooncol Lab, Padua, Italy

[13] CNR, Ist Cristallog, I-70126 Bari, Italy

[14] NCI, Womens Canc Sect, Mol Pharmacol Lab, Bethesda, MD 20892 USA

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

关键词：

CARCINOMA-CELL-LINE; H-PRUNE; N-MYC; NM23-H1; CANCER; GENE; EXPRESSION; PROTEIN; OVEREXPRESSION; METASTASIS;

D O I：

10.1038/srep01351

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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