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Semin Cancer Biol. 2016 Jun;37-38:36-50. doi: 10.1016/j.semcancer.2015.12.004. Epub 2015 Dec 23.

The relationship between the nucleolus and cancer: Current evidence and emerging paradigms.

Author information

1
Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, Croatia.
2
Pfizer Research & Development, 610 Main Street, Cambridge, MA 02139, USA.
3
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
4
Molecular and Cellular Biology Laboratory, Division of Basic Sciences, University of Crete Medical School, 71003 Heraklion, Greece; Institute of Molecular Biology & Biotechnology, Foundations of Research & Technology Hellas, Heraklion, Greece.
5
Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, Croatia. Electronic address: sinisa.volarevic@medri.uniri.hr.

Abstract

The nucleolus is the most prominent nuclear substructure assigned to produce ribosomes; molecular machines that are responsible for carrying out protein synthesis. To meet the increased demand for proteins during cell growth and proliferation the cell must increase protein synthetic capacity by upregulating ribosome biogenesis. While larger nucleolar size and number have been recognized as hallmark features of many tumor types, recent evidence has suggested that, in addition to overproduction of ribosomes, decreased ribosome biogenesis as well as qualitative changes in this process could also contribute to tumor initiation and cancer progression. Furthermore, the nucleolus has become the focus of intense attention for its involvement in processes that are clearly unrelated to ribosome biogenesis such as sensing and responding to endogenous and exogenous stressors, maintenance of genome stability, regulation of cell-cycle progression, cellular senescence, telomere function, chromatin structure, establishment of nuclear architecture, global regulation of gene expression and biogenesis of multiple ribonucleoprotein particles. The fact that dysregulation of many of these fundamental cellular processes may contribute to the malignant phenotype suggests that normal functioning of the nucleolus safeguards against the development of cancer and indicates its potential as a therapeutic approach. Here we review the recent advances made toward understanding these newly-recognized nucleolar functions and their roles in normal and cancer cells, and discuss possible future research directions.

KEYWORDS:

Cancer; Genome instability; Nucleolus; Ribosome biogenesis stress; p53

PMID:
26721423
DOI:
10.1016/j.semcancer.2015.12.004
[Indexed for MEDLINE]

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