title: Reprint of: Signaling the Unfolded Protein Response in primary brain cancers.
abstract: The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target. This article is part of a Special Issue entitled SI:ER stress.
authors.affiliation: Department of Neurosurgery, University Hospital Pontchaillou, Rennes, France; Inserm ERL440 "Oncogenesis, Stress, Signaling", Université de Rennes 1, Rennes, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Le Reste
authors.affiliation: Inserm ERL440 "Oncogenesis, Stress, Signaling", Université de Rennes 1, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Avril
authors.affiliation: Inserm ERL440 "Oncogenesis, Stress, Signaling", Université de Rennes 1, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
authors.affiliation: Department of Neurosurgery, University Hospital Pontchaillou, Rennes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Morandi
authors.affiliation: Inserm ERL440 "Oncogenesis, Stress, Signaling", Université de Rennes 1, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France. Electronic address: eric.chevet@inserm.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
keywords: Brain cancer; Endoplasmic reticulum; Glioma; Stress; UPR; Unfolded Protein Response