The nucleolus: an emerging target for cancer therapy

Trends Mol Med. 2013 Nov;19(11):643-54. doi: 10.1016/j.molmed.2013.07.005. Epub 2013 Aug 15.

Abstract

For over 100 years, pathologists have utilised an increase in size and number of nucleoli, the subnuclear site of ribosome synthesis, as a marker of aggressive tumours. Despite this, the contribution of the nucleolus and ribosomal RNA synthesis to cancer has been largely overlooked. This concept has recently changed with the demonstration that the nucleolus indirectly controls numerous other cellular functions, in particular, the cellular activity of the critical tumour suppressor protein, p53. Moreover, selective inhibition of ribosomal gene transcription in the nucleolus has been shown to be an effective therapeutic strategy to promote cancer-specific activation of p53. This article reviews the largely untapped potential of the nucleolus and ribosomal gene transcription as exciting new targets for cancer therapy.

Keywords: RNA polymerase I inhibitor; cancer therapy; nucleolar stress; nucleolus; p53; ribosomal gene transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Nucleolus / drug effects
  • Cell Nucleolus / genetics*
  • Cell Nucleolus / metabolism
  • DNA, Ribosomal / genetics
  • DNA, Ribosomal / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • DNA, Ribosomal