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Targeting the nucleolus for cancer intervention
- Source :
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1842(6):802-816
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
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.
- Subjects :
- p53
Nucleolus
Genes, myc
Ribosome biogenesis
MYC
Biology
Bioinformatics
DNA, Ribosomal
Ribosome
RNA polymerase III
Malignant transformation
RNA Polymerase I
Neoplasms
RNA polymerase I
CX-5461
Humans
Benzothiazoles
Naphthyridines
Transcription factor
Molecular Biology
Cancer
Retinoblastoma protein
Cell biology
Cell Transformation, Neoplastic
biology.protein
Molecular Medicine
Tumor Suppressor Protein p53
Nucleolar stress
Ribosomes
Cell Nucleolus
Subjects
Details
- ISSN :
- 09254439
- Volume :
- 1842
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Accession number :
- edsair.doi.dedup.....3d8877ab5a8fa73499f249a1086f59a5
- Full Text :
- https://doi.org/10.1016/j.bbadis.2013.12.009