文章：

肿瘤进展过程中mRNA翻译的可塑性和治疗耐药性

The plasticity of mRNA translation during cancer progression and therapy resistance

原文发布日期：2021-08-02

DOI: 10.1038/s41568-021-00380-y

类型: Review Article

开放获取: 否

英文摘要：

Translational control of mRNAs during gene expression allows cells to promptly and dynamically adapt to a variety of stimuli, including in neoplasia in response to aberrant oncogenic signalling (for example, PI3K–AKT–mTOR, RAS–MAPK and MYC) and microenvironmental stress such as low oxygen and nutrient supply. Such translational rewiring allows rapid, specific changes in the cell proteome that shape specific cancer phenotypes to promote cancer onset, progression and resistance to anticancer therapies. In this Review, we illustrate the plasticity of mRNA translation. We first highlight the diverse mechanisms by which it is regulated, including by translation factors (for example, eukaryotic initiation factor 4F (eIF4F) and eIF2), RNA-binding proteins, tRNAs and ribosomal RNAs that are modulated in response to aberrant intracellular pathways or microenvironmental stress. We then describe how translational control can influence tumour behaviour by impacting on the phenotypic plasticity of cancer cells as well as on components of the tumour microenvironment. Finally, we highlight the role of mRNA translation in the cellular response to anticancer therapies and its promise as a key therapeutic target.

摘要翻译： 

基因表达过程中对mRNA的翻译控制使细胞能够迅速动态地适应各种刺激，包括肿瘤发生过程中对异常致癌信号（如PI3K–AKT–mTOR、RAS–MAPK和MYC）及微环境压力（如低氧和营养供应）的响应。这种翻译重编程通过快速特异地改变细胞蛋白质组，塑造特定癌症表型，从而促进癌症的发生发展及抗癌治疗耐受。本文阐述了mRNA翻译的可塑性，首先重点分析了其调控机制的多样性——包括翻译因子（如真核起始因子4F和eIF2）、RNA结合蛋白、tRNA及rRNA如何响应异常细胞内通路或微环境压力而发生调节；继而探讨了翻译控制如何通过影响癌细胞表型可塑性与肿瘤微环境组成成分调控肿瘤行为；最后强调了mRNA翻译在细胞应对抗癌治疗中的重要作用及其作为关键治疗靶点的潜力。

原文链接：

The plasticity of mRNA translation during cancer progression and therapy resistance