Targeting the nucleolus for cancer intervention

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Review

Quin, Jaclyn E.^1,2  Devlin, Jennifer R.^1,2  Cameron, Donald¹  Hannan, Kate M.^1,2  Pearson, Richard B.^1,2,3  Hannan, Ross D.^1,2,3,4,5 

[1] Peter MacCallum Canc Ctr, Oncogen Signalling & Growth Control Program, Melbourne, Vic 8006, Australia

[2] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3052, Australia

[3] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia

[4] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia

[5] Univ Queensland, Sch Biomed Sci, St Lucia, Qld, Australia

关键词: Cancer;    Ribosome biogenesis;    Nucleolar stress;    CX-5461;    p53;    MYC;   

DOI  :  10.1016/j.bbadis.2013.12.009

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free