Protein synthesis control in cancer: selectivity and therapeutic targeting

• Published in: The EMBO journal 2022-04, Vol.41 (8), p.e109823-n/a
• Main Authors: Kovalski, Joanna R, Kuzuoglu‐Ozturk, Duygu, Ruggero, Davide
• Format: Article
• Language: English
• Subjects: Cancer; Carcinogenesis; Cell survival; EMBO03; EMBO32; Humans; Neoplasms - drug therapy; Neoplasms - genetics; New technology; Nucleotide sequence; Protein Biosynthesis; Protein synthesis; Proteins; Review; RNA, Messenger - metabolism; RNA-binding protein; Selectivity; Structural members; Survival; Therapeutic targets; Transformed cells; Translation; translation and protein quality; translation inhibitors; translational control; Tumor Microenvironment; Tumorigenesis
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.2021109823

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. Graphical Abstract This review provides an overview of the cellular and molecular mechanisms cancer cells use to adjust mRNA translation and protein synthesis in response to internal and external demands of a dynamic tumor microenvironment.