title: Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update.
abstract: The endoplasmic reticulum (ER)-induced unfolded protein response (UPR) is an adaptive mechanism that is activated upon accumulation of misfolded proteins in the ER and aims at restoring ER homeostasis. In the past 10 years, the UPR has emerged as an important actor in the different phases of tumor growth. The UPR is transduced by three major ER resident stress sensors, which are protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme-1 (IRE1). The signaling pathways elicited by those stress sensors have connections with metabolic pathways and with other plasma membrane receptor signaling networks. As such, the ER has an essential position as a signal integrator in the cell and is instrumental in the different phases of tumor progression. Herein, we describe and discuss the characteristics of an integrated signaling network that might condition the UPR biological outputs in a tissue- or stress-dependent manner. We discuss these issues in the context of the pathophysiological roles of UPR signaling in cancers.
authors.affiliation: University of Lyon, Lyon, France, and UMR CNRS 5286 - INSERM 1052 - University of Lyon, Cancer Research Center of Lyon, Team ER Stress and Tumorigenesis, Lyon, France; eric.chevet@inserm.fr serge.manie@lyon.unicancer.fr.
authors.forename: Serge N
authors.initials: SN
authors.lastname: Manié
authors.affiliation: University of Lyon, Lyon, France, and UMR CNRS 5286 - INSERM 1052 - University of Lyon, Cancer Research Center of Lyon, Team ER Stress and Tumorigenesis, Lyon, France;
authors.forename: Justine
authors.initials: J
authors.lastname: Lebeau
authors.affiliation: Inserm U1053, Team Endoplasmic Reticulum Stress and Cancer, Université de Bordeaux, Bordeaux, France; and Centre Régional de Lutte Contre le Cancer Eugène Marquis, Rennes, France eric.chevet@inserm.fr serge.manie@lyon.unicancer.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D056811:Unfolded Protein Response / Q000502:physiology*
keywords: cancer; endoplasmic reticulum; metabolism; signaling; stress