Protein synthesis control in cancer: selectivity and therapeutic targeting

EMBO J. 2022 Apr 19;41(8):e109823. doi: 10.15252/embj.2021109823. Epub 2022 Mar 22.

Abstract

Translational control of mRNAs is a point of convergence for many oncogenic signals through which cancer cells tune protein expression in tumorigenesis. Cancer cells rely on translational control to appropriately adapt to limited resources while maintaining cell growth and survival, which creates a selective therapeutic window compared to non-transformed cells. In this review, we first discuss how cancer cells modulate the translational machinery to rapidly and selectively synthesize proteins in response to internal oncogenic demands and external factors in the tumor microenvironment. We highlight the clinical potential of compounds that target different translation factors as anti-cancer therapies. Next, we detail how RNA sequence and structural elements interface with the translational machinery and RNA-binding proteins to coordinate the translation of specific pro-survival and pro-growth programs. Finally, we provide an overview of the current and emerging technologies that can be used to illuminate the mechanisms of selective translational control in cancer cells as well as within the microenvironment.

Keywords: cancer; protein synthesis; translation and protein quality; translation inhibitors; translational control.

Publication types

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

MeSH terms

  • Carcinogenesis
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Protein Biosynthesis*
  • RNA, Messenger / metabolism
  • Tumor Microenvironment

Substances

  • RNA, Messenger