Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Blood. 2010 Mar 18;115(11):2127-35. doi: 10.1182/blood-2009-09-220020. Epub 2010 Jan 14.
The dysregulation of protein synthesis evident in the transformed phenotype has opened up a burgeoning field of research in cancer biology. Translation initiation has recently been shown to be a common downstream target of signal transduction pathways deregulated in cancer and initiated by mutated/overexpressed oncogenes and tumor suppressors. The overexpression and/or activation of proteins involved in translation initiation such as eIF4E, mTOR, and eIF4G have been shown to induce a malignant phenotype. Therefore, understanding the mechanisms that control protein synthesis is emerging as an exciting new research area with significant potential for developing innovative therapies. This review highlights molecules that are activated or dysregulated in hematologic malignancies, and promotes the transformed phenotype through the deregulation of protein synthesis. Targeting these proteins with small molecule inhibitors may constitute a novel therapeutic approach in the treatment of cancer.
在转化表型中明显存在的蛋白质合成失调,为癌症生物学的研究开辟了一个新兴领域。最近的研究表明,翻译起始是癌症中信号转导途径失调的一个常见下游靶点,而这些信号转导途径是由突变/过表达的癌基因和肿瘤抑制因子启动的。已证实参与翻译起始的蛋白质(如 eIF4E、mTOR 和 eIF4G)的过表达和/或激活会诱导恶性表型。因此,了解控制蛋白质合成的机制正在成为一个令人兴奋的新研究领域,具有开发创新疗法的巨大潜力。本综述强调了在血液恶性肿瘤中被激活或失调的分子,并通过蛋白质合成的失调促进转化表型。用小分子抑制剂靶向这些蛋白质可能构成癌症治疗的一种新的治疗方法。