title: Endoplasmic reticulum proteostasis in glioblastoma-From molecular mechanisms to therapeutic perspectives.
abstract: Cellular stress induced by the accumulation of misfolded proteins at the endoplasmic reticulum (ER) is a central feature of secretory cells and is observed in many tissues in various diseases, including cancer, diabetes, obesity, and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the cytosol and nucleus to restore proteostasis. In the past decade, ER stress has emerged as a major pathway in remodeling gene expression programs that either prevent transformation or provide selective advantage in cancer cells. Controlled by the formation of a dynamic scaffold onto which many regulatory components assemble, UPR signaling is a highly regulated process that leads to an integrated reprogramming of the cell. In this Review, we provide an overview of the regulatory mechanisms underlying UPR signaling and how this pathway modulates cancer progression, particularly the aggressiveness and chemotherapeutic resistance exhibited by glioblastoma, a form of brain cancer. We also discuss the emerging cross-talk between the UPR and related metabolic processes to ensure maintenance of proteostasis, and we highlight possible therapeutic opportunities for targeting the pathway with small molecules.
authors.affiliation: INSERM U1242, Chemistry, Oncogenesis, Stress Signaling, Université de Rennes 1, Rennes 35000, France.|Centre de Lutte Contre le Cancer Eugène Marquis, Rennes 35042, France.
authors.forename: Joanna
authors.identifier: http://orcid.org/0000-0002-4539-9946
authors.initials: J
authors.lastname: Obacz
authors.affiliation: INSERM U1242, Chemistry, Oncogenesis, Stress Signaling, Université de Rennes 1, Rennes 35000, France.|Centre de Lutte Contre le Cancer Eugène Marquis, Rennes 35042, France.
authors.forename: Tony
authors.identifier: http://orcid.org/0000-0002-1129-8514
authors.initials: T
authors.lastname: Avril
authors.affiliation: INSERM U1242, Chemistry, Oncogenesis, Stress Signaling, Université de Rennes 1, Rennes 35000, France.|Centre de Lutte Contre le Cancer Eugène Marquis, Rennes 35042, France.|Department of Neurosurgery, University Hospital Pontchaillou, Rennes 35000, France.
authors.forename: Pierre-Jean
authors.identifier: http://orcid.org/0000-0003-4673-5697
authors.initials: PJ
authors.lastname: Le Reste
authors.affiliation: Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile.|Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.|Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, 1027 Independencia, P.O. Box 70086, Santiago, Chile.
authors.forename: Hery
authors.identifier: http://orcid.org/0000-0002-6846-558X
authors.initials: H
authors.lastname: Urra
authors.affiliation: INSERM U1242, Chemistry, Oncogenesis, Stress Signaling, Université de Rennes 1, Rennes 35000, France.|Centre de Lutte Contre le Cancer Eugène Marquis, Rennes 35042, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
authors.affiliation: Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile.|Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.|Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, 1027 Independencia, P.O. Box 70086, Santiago, Chile.|Buck Institute for Research on Aging, Novato, CA 94945, USA.|Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
authors.affiliation: INSERM U1242, Chemistry, Oncogenesis, Stress Signaling, Université de Rennes 1, Rennes 35000, France. eric.chevet@inserm.fr.|Centre de Lutte Contre le Cancer Eugène Marquis, Rennes 35042, France.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0001-5855-4522
authors.initials: E
authors.lastname: Chevet
mesh_terms: D000818:Animals; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction; D056811:Unfolded Protein Response