Oncotarget

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Molecules that target nucleophosmin for cancer treatment: an update

Adele Di Matteo, Mimma Franceschini, Sara Chiarella, Serena Rocchio, Carlo Travaglini-Allocatelli and Luca Federici _

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Oncotarget. 2016; 7:44821-44840. https://doi.org/10.18632/oncotarget.8599

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Abstract

Adele Di Matteo1, Mimma Franceschini2,3, Sara Chiarella2,3, Serena Rocchio4, Carlo Travaglini-Allocatelli4 and Luca Federici2,3

1 Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Rome, Italy

2 Dipartimento di Scienze Mediche, Orali e Biotecnologiche, Università di Chieti “G. d’Annunzio”, Chieti, Italy

3 Ce.S.I.-MeT Centro Scienze dell’Invecchiamento-Medicina Traslazionale, Università di Chieti “G. d’Annunzio”, Chieti, Italy

4 Dipartimento di Scienze Biochimiche “A. Rossi Fanelli”, Università di Roma “Sapienza”, Rome, Italy

Correspondence to:

Luca Federici, email:

Adele Di Matteo, email:

Keywords: nucleophosmin, B23, acute myeloid leukemia, solid tumours, targeted therapy

Received: January 05, 2016 Accepted: March 28, 2016 Published: April 05, 2016

Abstract

Nucleophosmin is a highly and ubiquitously expressed protein, mainly localized in nucleoli but able to shuttle between nucleus and cytoplasm. Nucleophosmin plays crucial roles in ribosome maturation and export, centrosome duplication, cell cycle progression, histone assembly and response to a variety of stress stimuli. Much interest in this protein has arisen in the past ten years, since the discovery of heterozygous mutations in the terminal exon of the NPM1 gene, which are the most frequent genetic alteration in acute myeloid leukemia. Nucleophosmin is also frequently overexpressed in solid tumours and, in many cases, its overexpression correlates with mitotic index and metastatization. Therefore it is considered as a promising target for the treatment of both haematologic and solid malignancies. NPM1 targeting molecules may suppress different functions of the protein, interfere with its subcellular localization, with its oligomerization properties or drive its degradation. In the recent years, several such molecules have been described and here we review what is currently known about them, their interaction with nucleophosmin and the mechanistic basis of their toxicity. Collectively, these molecules exemplify a number of different strategies that can be adopted to target nucleophosmin and we summarize them at the end of the review.


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PII: 8599