The plasticity of mRNA translation during cancer progression and therapy resistance

被引:144
作者
Fabbri, Lucilla [1 ,2 ,3 ]
Chakraborty, Alina [1 ,2 ,3 ]
Robert, Caroline [4 ,5 ,6 ]
Gagner, Stephan [1 ,2 ,3 ,6 ]
机构
[1] PSL Res Univ, Inst Curie, CNRS, UMR3348,INSERM,U1278, Orsay, France
[2] Univ Paris Sud, Univ Paris Saclay, CNRS, UMR3348,INSERM,U1278, Orsay, France
[3] Equipe Labellisee Ligue Natl Canc, Orsay, France
[4] INSERM, U981, Gustave Roussy Canc Campus, Villejuif, France
[5] Univ Paris Sud, Univ Paris Saclay, Le Kremlin Bicetre, France
[6] Dermatooncology, Gustave Roussy Canc Campus, Villejuif, France
关键词
IRES-MEDIATED TRANSLATION; INITIATION-FACTOR; 4E; CAP-BINDING PROTEIN; METHYLTRANSFERASE METTL3 PROMOTES; INTEGRATED STRESS-RESPONSE; GENE-EXPRESSION; STEM-CELLS; DEPENDENT TRANSLATION; BREAST-CANCER; C-MYC;
D O I
10.1038/s41568-021-00380-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The translational control of mRNAs during gene expression allows rapid, specific changes in the cell proteome. This Review describes the mechanisms underlying changes in mRNA translation in response to oncogenic signalling and microenvironmental stress, and how these changes can promote cancer onset, progression and resistance to anticancer therapies. 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.
引用
收藏
页码:558 / 577
页数:20
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