title: Targeting the angio-proteostasis network: Combining the forces against cancer.
abstract: The VEGF family of pro-angiogenic factors has represented a pillar for targeted cancer therapy for more than a decade. In comparison, the field of protein homeostasis (proteostasis) focusing on the Unfolded Protein Response (UPR), an endoplasmic reticulum (ER) stress-induced signaling cascade, has just recently emerged as an attractive anti-cancer approach. Recent findings suggest that both signaling pathways are incontestably interrelated to ensure cell survival. Herein, we summarize recent findings that demonstrate how these two fundamental aspects of cancer cell survival intersect and provide genetic and pharmacological evidence of the interplay between angiogenic factors such as VEGF-A or PlGF and the individual members of the UPR such as IRE1, PERK and ATF6. We further describe how this interaction does not only affect the cancer cells, but also the surrounding microenvironmental niche that is also involved in tumor progression. Furthermore, by summarizing the recent therapeutic implications of both anti-angiogenic and proteostatic approaches, we emphasize how these novel findings could be used synergistically to improve cancer therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Devisscher
authors.affiliation: Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University Medical School, Aachen, Germany.
authors.forename: Margherita
authors.initials: M
authors.lastname: Vieri
authors.affiliation: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Logue
authors.affiliation: Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University Medical School, Aachen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.affiliation: Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Anja
authors.initials: A
authors.lastname: Geerts
authors.affiliation: Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: van Vlierberghe
authors.affiliation: INSERM ERL440, Oncogenesis, Stress and Signaling, Université Rennes 1, Rennes, France; Centre de Lutte Contre Le Cancer Eugène Marquis, Rennes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.affiliation: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Gorman
authors.affiliation: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Afshin
authors.initials: A
authors.lastname: Samali
authors.affiliation: Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University Medical School, Aachen, Germany. Electronic address: bkharabi@ukaachen.de.
authors.forename: Behzad
authors.initials: B
authors.lastname: Kharabi Masouleh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D004357:Drug Synergism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment; D056811:Unfolded Protein Response / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Cancer; IRE1; PlGF; Unfolded protein response; VEGF