کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2838576 | 1165029 | 2013 | 12 صفحه PDF | دانلود رایگان |

• RNA polymerase I (Pol I) transcription and ribosome production in the nucleolus is invariably upregulated in cancer.
• In addition to ribosome production, the nucleolus controls other cellular functions, including cell cycle progression, DNA replication and repair, stress signalling, cell survival, senescence, and induction of apoptosis.
• Small molecule inhibitors of Pol I transcription induce a nucleolar stress response to promote cancer-specific activation of the tumour suppressor p53.
• Pol I transcription inhibitors are currently entering Phase I clinical trials in cancer treatment.
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.
Journal: - Volume 19, Issue 11, November 2013, Pages 643–654