title: Stress-mediated translational control in cancer cells.
abstract: 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.
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L4, Canada; Department of Pathology, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Leprivier
authors.affiliation: Department of Life Science, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Rotblat
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L4, Canada; Department of Pathology, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
authors.forename: Debjit
authors.initials: D
authors.lastname: Khan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Jan
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L4, Canada; Department of Pathology, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada. Electronic address: psor@mail.ubc.ca.
authors.forename: Poul H
authors.initials: PH
authors.lastname: Sorensen
mesh_terms: D000818:Animals; D004249:DNA Damage; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D015852:Eukaryotic Initiation Factor-2; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Stress response; Tumor adaptation; eEF2K; eIF2alpha; mRNA translation control; mTORC1