Helen Diller Cancer Center, School of Medicine, University of California, San Francisco, CA 94158, USA.
Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2):a012336. doi: 10.1101/cshperspect.a012336.
The link between perturbations in translational control and cancer etiology is becoming a primary focus in cancer research. It has now been established that genetic alterations in several components of the translational apparatus underlie spontaneous cancers as well as an entire class of inherited syndromes known as "ribosomopathies" associated with increased cancer susceptibility. These discoveries have illuminated the importance of deregulations in translational control to very specific cellular processes that contribute to cancer etiology. In addition, a growing body of evidence supports the view that deregulation of translational control is a common mechanism by which diverse oncogenic pathways promote cellular transformation and tumor development. Indeed, activation of these key oncogenic pathways induces rapid and dramatic translational reprogramming both by increasing overall protein synthesis and by modulating specific mRNA networks. These translational changes promote cellular transformation, impacting almost every phase of tumor development. This paradigm represents a new frontier in the multihit model of cancer formation and offers significant promise for innovative cancer therapies. Current research, in conjunction with cutting edge technologies, will further enable us to explore novel mechanisms of translational control, functionally identify translationally controlled mRNA groups, and unravel their impact on cellular transformation and tumorigenesis.
在翻译控制的干扰与癌症病因之间的联系正成为癌症研究的主要焦点。现在已经确定,翻译机制的几个组成部分的遗传改变是自发性癌症以及一类被称为“核糖体病”的遗传性疾病的基础,这些疾病与癌症易感性增加有关。这些发现强调了翻译控制的失调对特定细胞过程的重要性,这些过程有助于癌症的发生。此外,越来越多的证据支持这样一种观点,即翻译控制的失调是不同致癌途径促进细胞转化和肿瘤发展的常见机制。事实上,这些关键致癌途径的激活通过增加整体蛋白质合成和调节特定的 mRNA 网络来快速和显著地重新编程翻译。这些翻译变化促进了细胞转化,几乎影响了肿瘤发展的每一个阶段。这一范例代表了癌症形成的多击模型的一个新前沿,并为创新的癌症治疗提供了巨大的希望。目前的研究结合前沿技术,将使我们能够进一步探索翻译控制的新机制,从功能上鉴定受翻译控制的 mRNA 组,并揭示它们对细胞转化和肿瘤发生的影响。