title: Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.
abstract: Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.
authors.affiliation: 1] Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143, USA [2] Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Dipartimento di Biologia e Biotecnologie, Università La Sapienza, 00185 Rome, Italy [3].
authors.forename: Daniela
authors.initials: D
authors.lastname: Annibali
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain [3].
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Whitfield
authors.affiliation: Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Dipartimento di Biologia e Biotecnologie, Università La Sapienza, 00185 Rome, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Favuzzi
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Toni
authors.initials: T
authors.lastname: Jauset
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Erika
authors.initials: E
authors.lastname: Serrano
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cuartas
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Redondo-Campos
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Folch
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Gonzàlez-Juncà
authors.affiliation: 1] Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143, USA [2] Department of Biochemistry, Sanger Building, University of Cambridge, Cambridge CB2 1QW, UK.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Sodir
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Massó-Vallés
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Beaulieu
authors.affiliation: Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Lamorna B
authors.initials: LB
authors.lastname: Swigart
authors.affiliation: UCD School of Biomolecular &Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Mc Gee
authors.affiliation: Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Dipartimento di Biologia e Biotecnologie, Università La Sapienza, 00185 Rome, Italy.
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Somma
authors.affiliation: Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Dipartimento di Biologia e Biotecnologie, Università La Sapienza, 00185 Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Nasi
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain [3] Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Seoane
authors.affiliation: Department of Biochemistry, Sanger Building, University of Cambridge, Cambridge CB2 1QW, UK.
authors.forename: Gerard I
authors.initials: GI
authors.lastname: Evan
authors.affiliation: 1] Vall d'Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d'Hebron, 08035 Barcelona, Spain [2] Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Soucek
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001254:Astrocytoma / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D064593:Heterografts; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000502:physiology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000502:physiology; D044764:Ubiquitin-Activating Enzymes / Q000502:physiology
chemical_list: C489427:MYC protein, human; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C000602871:SAE1 protein, mouse; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse; C470299:SAE1 protein, human; D044764:Ubiquitin-Activating Enzymes