Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1842, Issue 6, Pages 802-816Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2013.12.009
Keywords
Cancer; Ribosome biogenesis; Nucleolar stress; CX-5461; p53; MYC
Funding
- NHMRC of Australia [166908, 251688]
- RBP [I043884, 509087, 400116]
- Prostate Cancer Foundation of Australia
- RBP
- Leukaemia Foundation of Australia
- NHMRC (Research Fellowships
- Australian Federal Government (Australian Postgraduate Award)
- Leukaemia Foundation of Australia (Postgraduate Research Award
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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 Ito 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. (C) 2013 Elsevier B.V. All rights reserved.
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