Cylene Pharmaceuticals, San Diego, California, USA.
Annu Rev Pharmacol Toxicol. 2010;50:131-56. doi: 10.1146/annurev.pharmtox.010909.105844.
The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that inactivate tumor suppressors, hyperactivate oncogenes, and upregulate protein kinases, all of which promote Pol I transcription and drive cell proliferation. The intimate balance between Pol I transcription and growth-factor signaling is perturbed in cancer cells, indicating that upregulation of rRNA synthesis is mandatory for all tumors. Though the emerging picture of transcriptional regulation reveals an unexpected level of complexity, we are beginning to understand the multiple links between rRNA biogenesis and cancer. In this review, we discuss experimental data and potential strategies to downregulate rRNA synthesis and induce an antiproliferative response in cancer cells.
核仁中的 RNA 聚合酶 I (Pol I) 转录机制是一个关键的汇聚点，它汇集和整合来自细胞信号级联的大量信息，以调节核糖体的产生，进而指导细胞生长和增殖。癌细胞通常携带有失活肿瘤抑制因子、过度激活癌基因和上调蛋白激酶的突变，所有这些都促进了 Pol I 转录并驱动细胞增殖。Pol I 转录和生长因子信号之间的紧密平衡在癌细胞中被打破，这表明 rRNA 合成的上调对于所有肿瘤都是必需的。尽管转录调控的新图景揭示了出人意料的复杂程度，但我们开始理解 rRNA 生物发生与癌症之间的多种联系。在这篇综述中，我们讨论了实验数据和潜在的策略，以下调 rRNA 合成并在癌细胞中诱导抗增殖反应。
