Cancer Plasticity: The Role of mRNA Translation

Trends Cancer. 2021 Feb;7(2):134-145. doi: 10.1016/j.trecan.2020.09.005. Epub 2020 Oct 13.

Abstract

Tumor progression is associated with dedifferentiated histopathologies concomitant with cancer cell survival within a changing, and often hostile, tumor microenvironment. These processes are enabled by cellular plasticity, whereby intracellular cues and extracellular signals are integrated to enable rapid shifts in cancer cell phenotypes. Cancer cell plasticity, at least in part, fuels tumor heterogeneity and facilitates metastasis and drug resistance. Protein synthesis is frequently dysregulated in cancer, and emerging data suggest that translational reprograming collaborates with epigenetic and metabolic programs to effectuate phenotypic plasticity of neoplasia. Herein, we discuss the potential role of mRNA translation in cancer cell plasticity, highlight emerging histopathological correlates, and deliberate on how this is related to efforts to improve understanding of the complex tumor ecology.

Keywords: cancer plasticity; mRNA translation; metabolism; protein synthesis; stromal–epithelial interactions; therapy resistance; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Plasticity / drug effects
  • Cell Plasticity / genetics*
  • Disease Progression
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Eukaryotic Initiation Factor-2 / genetics
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-4F / genetics
  • Eukaryotic Initiation Factor-4F / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genetic Heterogeneity
  • Humans
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Oxidative Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / genetics*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Warburg Effect, Oncologic / drug effects

Substances

  • Antineoplastic Agents
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-4F