Stress-mediated translational control in cancer cells

• Published in: Biochimica et biophysica acta Vol. 1849; no. 7; pp. 845 - 860
• Main Authors: Leprivier, Gabriel, Rotblat, Barak, Khan, Debjit, Jan, Eric, Sorensen, Poul H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2015
• Subjects: Animals; DNA Damage; eEF2K; eIF2alpha; Eukaryotic Initiation Factor-2 - genetics; Eukaryotic Initiation Factor-2 - metabolism; Humans; Mechanistic Target of Rapamycin Complex 1; mRNA translation control; mTORC1; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Protein Biosynthesis; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Stress response; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Tumor adaptation; eEF2K; Tumor adaptation; eIF2alpha; mRNA translation control; Stress response; mTORC1
• ISSN: 1874-9399; 0006-3002; 1876-4320
• DOI: 10.1016/j.bbagrm.2014.11.002

Tumor cells are continually subjected to diverse stress conditions of the tumor microenvironment, including hypoxia, nutrient deprivation, and oxidative or genotoxic stress. Tumor cells must evolve adaptive mechanisms to survive these conditions to ultimately drive tumor progression. Tight control of mRNA translation is critical for this response and the adaptation of tumor cells to such stress forms. This proceeds though a translational reprogramming process which restrains overall translation activity to preserve energy and nutrients, but which also stimulates the selective synthesis of major stress adaptor proteins. Here we present the different regulatory signaling pathways which coordinate mRNA translation in the response to different stress forms, including those regulating eIF2α, mTORC1 and eEF2K, and we explain how tumor cells hijack these pathways for survival under stress. Finally, mechanisms for selective mRNA translation under stress, including the utilization of upstream open reading frames (uORFs) and internal ribosome entry sites (IRESes) are discussed in the context of cell stress. This article is part of a Special Issue entitled: Translation and Cancer. •Global mRNA translation is reduced in response to stresses in most cancer cells.•Selective translation is induced by cell stress through usage of uORFs and IRESes.•Selective translation contributes to tumor adaptation under cell stress.•eIF2α, mTORC1, and eEF2K are major translational regulators in the stress response.