Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
EMBO J. 2022 Apr 19;41(8):e109823. doi: 10.15252/embj.2021109823. Epub 2022 Mar 22.
Translational control of mRNAs is a point of convergence for many oncogenic signals through which cancer cells tune protein expression in tumorigenesis. Cancer cells rely on translational control to appropriately adapt to limited resources while maintaining cell growth and survival, which creates a selective therapeutic window compared to non-transformed cells. In this review, we first discuss how cancer cells modulate the translational machinery to rapidly and selectively synthesize proteins in response to internal oncogenic demands and external factors in the tumor microenvironment. We highlight the clinical potential of compounds that target different translation factors as anti-cancer therapies. Next, we detail how RNA sequence and structural elements interface with the translational machinery and RNA-binding proteins to coordinate the translation of specific pro-survival and pro-growth programs. Finally, we provide an overview of the current and emerging technologies that can be used to illuminate the mechanisms of selective translational control in cancer cells as well as within the microenvironment.
mRNA 的翻译调控是许多致癌信号的交汇点，癌细胞通过这些信号在肿瘤发生过程中调节蛋白质表达。癌细胞依靠翻译调控来适当地适应有限的资源，同时保持细胞生长和存活，这与非转化细胞相比创造了一个选择性的治疗窗口。在这篇综述中，我们首先讨论了癌细胞如何调节翻译机制，以快速和选择性地合成蛋白质，以响应内部致癌需求和肿瘤微环境中的外部因素。我们强调了靶向不同翻译因子的化合物作为抗癌疗法的临床潜力。接下来，我们详细介绍了 RNA 序列和结构元件如何与翻译机制和 RNA 结合蛋白相互作用，以协调特定的生存和促生长程序的翻译。最后，我们概述了目前和新兴的技术，这些技术可以用来阐明癌细胞内以及微环境中选择性翻译调控的机制。
