The plasticity of mRNA translation during cancer progression and therapy resistance.
Nat Rev Cancer
; 21(9): 558-577, 2021 09.
Article
in En
| MEDLINE
| ID: mdl-34341537
ABSTRACT
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.
Full text:
1
Database:
MEDLINE
Main subject:
Protein Biosynthesis
/
RNA, Messenger
/
Drug Resistance, Neoplasm
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Rev Cancer
Journal subject:
NEOPLASIAS
Year:
2021
Type:
Article
Affiliation country:
France