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Biochim Biophys Acta. 2014 Jun;1842(6):802-16. doi: 10.1016/j.bbadis.2013.12.009. Epub 2014 Jan 2.

Targeting the nucleolus for cancer intervention.

Author information

1
Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia.
2
Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
3
Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
4
Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia; School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia. Electronic address: ross.hannan@petermac.org.

Abstract

The contribution of the nucleolus to cancer is well established with respect to its traditional role in facilitating ribosome biogenesis and proliferative capacity. More contemporary studies however, infer that nucleoli contribute a much broader role in malignant transformation. Specifically, extra-ribosomal functions of the nucleolus position it as a central integrator of cellular proliferation and stress signaling, and are emerging as important mechanisms for modulating how oncogenes and tumor suppressors operate in normal and malignant cells. The dependence of certain tumor cells to co-opt nucleolar processes to maintain their cancer phenotypes has now clearly been demonstrated by the application of small molecule inhibitors of RNA Polymerase I to block ribosomal DNA transcription and disrupt nucleolar function (Bywater et al., 2012 [1]). These drugs, which selectively kill tumor cells in vivo while sparing normal cells, have now progressed to clinical trials. It is likely that we have only just begun to scratch the surface of the potential of the nucleolus as a new target for cancer therapy, with "suppression of nucleolar stress" representing an emerging "hallmark" of cancer. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.

KEYWORDS:

CX-5461; Cancer; MYC; Nucleolar stress; Ribosome biogenesis; p53

PMID:
24389329
DOI:
10.1016/j.bbadis.2013.12.009
[Indexed for MEDLINE]
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