Translation initiation in cancer at a glance.

Rachael C L Smith,Constantinos Alexandrou,Georgios Kanellos,John R P Knight,Nikola Vlahov,Owen J Sansom,Anne E Willis

doi:10.1242/jcs.248476

Abstract

Cell division, differentiation and function are largely dependent on accurate proteome composition and regulated gene expression. To control this, protein synthesis is an intricate process governed by upstream signalling pathways. Eukaryotic translation is a multistep process and can be separated into four distinct phases: initiation, elongation, termination and recycling of ribosomal subunits. Translation initiation, the focus of this article, is highly regulated to control the activity and/or function of eukaryotic initiation factors (eIFs) and permit recruitment of mRNAs to the ribosomes. In this Cell Science at a Glance and accompanying poster, we outline the mechanisms by which tumour cells alter the process of translation initiation and discuss how this benefits tumour formation, proliferation and metastasis.

Highlights

In healthy cells, control of translation initiation is required for homeostasis, which is mediated through the production of key proteins that underpin essential cellular processes
Cancers exploit the mechanisms by which translation is regulated in order to generate a proteome that is conducive with proliferation, invasion or migration
This can result from an increase in total protein synthesis rates by elevated expression of specific eukaryotic initiation factors (eIFs), but from the effects of signalling to translation by pathways that converge on, for example, eIF2α and the 4E-BPs

Summary

Introduction

Control of translation initiation is required for homeostasis, which is mediated through the production of key proteins that underpin essential cellular processes. The presence of uORFs on the PD-L1 mRNA facilitates increased PD-L1 synthesis following stress induced P-eIF2α, a mechanism that lung cancer cells were shown to employ in order to evade immune attack (Suresh et al, 2020).

Results

Conclusion