» Articles » PMID: 27058426

Molecules That Target Nucleophosmin for Cancer Treatment: an Update

Overview
Journal Oncotarget
Specialty Oncology
Date 2016 Apr 9
PMID 27058426
Citations 36
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Abnormalities in Chromosomes 5 and 7 in Myelodysplastic Syndrome and Acute Myeloid Leukemia.

Kendrick T, Buic D, Fuller K, Erber W Ann Lab Med. 2025; 45(2):133-145.

PMID: 39774131 PMC: 11788707. DOI: 10.3343/alm.2024.0477.


Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression.

Jang H, Min H, Kang Y, Boo H, Kim J, Ahn J Nat Commun. 2024; 15(1):4909.

PMID: 38851766 PMC: 11162468. DOI: 10.1038/s41467-024-49199-9.


Cancer-Stem-Cell Phenotype-Guided Discovery of a Microbiota-Inspired Synthetic Compound Targeting NPM1 for Leukemia.

Algar S, Vazquez-Villa H, Aguilar-Garrido P, Navarro-Aguadero M, Velasco-Estevez M, Sanchez-Merino A JACS Au. 2024; 4(5):1786-1800.

PMID: 38818079 PMC: 11134387. DOI: 10.1021/jacsau.3c00682.


RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation.

Suh Y, Lee J, George J, Seol D, Jeong K, Oh S Br J Cancer. 2024; 130(9):1571-1584.

PMID: 38467827 PMC: 11059174. DOI: 10.1038/s41416-024-02642-6.


NPM promotes hepatotoxin-induced fibrosis by inhibiting ROS-induced apoptosis of hepatic stellate cells and upregulating lncMIAT-induced TGF-β2.

Ding X, Zhu X, Xu D, Li S, Yang Q, Feng X Cell Death Dis. 2023; 14(8):575.

PMID: 37648688 PMC: 10469196. DOI: 10.1038/s41419-023-06043-0.


References
1.
Solares A, Santana A, Baladron I, Valenzuela C, Gonzalez C, Diaz A . Safety and preliminary efficacy data of a novel casein kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies. BMC Cancer. 2009; 9:146. PMC: 2689241. DOI: 10.1186/1471-2407-9-146. View

2.
Roussel P, Hernandez-Verdun D . Identification of Ag-NOR proteins, markers of proliferation related to ribosomal gene activity. Exp Cell Res. 1994; 214(2):465-72. DOI: 10.1006/excr.1994.1283. View

3.
Marasco D, Scognamiglio P . Identification of inhibitors of biological interactions involving intrinsically disordered proteins. Int J Mol Sci. 2015; 16(4):7394-412. PMC: 4425024. DOI: 10.3390/ijms16047394. View

4.
Herrera J, Savkur R, Olson M . The ribonuclease activity of nucleolar protein B23. Nucleic Acids Res. 1995; 23(19):3974-9. PMC: 307319. DOI: 10.1093/nar/23.19.3974. View

5.
Bertwistle D, Sugimoto M, Sherr C . Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Mol Cell Biol. 2004; 24(3):985-96. PMC: 321449. DOI: 10.1128/MCB.24.3.985-996.2004. View