title: Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth.
abstract: DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT3A-binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3γ interaction such as a biomarker whose the presence level is associated with a poor survival prognosis and with a poor prognosis of response to the conventional chemotherapeutic treatment of glioblastoma multiforme (radiation plus temozolomide). Our data also demonstrates that the disruption of DNMT3A/ISGF3γ interactions increases the efficiency of chemotherapeutic treatment on established tumors in mice. Thus, our data opens a promising and innovative alternative to the development of specific DNMT inhibitors.
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.; present address: Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm 17176, Sweden.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Cheray
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Pacaud
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.
authors.forename: Arulraj
authors.initials: A
authors.lastname: Nadaradjane
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.
authors.forename: Lisa
authors.initials: L
authors.lastname: Oliver
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.; LaBCT, Institut de Cancérologie de l'Ouest, Boulevard J Monod, 44805 Nantes, Saint Herblain Cedex, France.
authors.forename: François M
authors.initials: FM
authors.lastname: Vallette
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.; LaBCT, Institut de Cancérologie de l'Ouest, Boulevard J Monod, 44805 Nantes, Saint Herblain Cedex, France.; Member of the "Réseau Epigénétique du Canceropôle Grand-Ouest".
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Cartron
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors*; D000090205:DNA Methyltransferase 3A; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000037:antagonists & inhibitors*; D051379:Mice; D008819:Mice, Nude; D016019:Survival Analysis; D000077204:Temozolomide; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D003606:Dacarbazine; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000077204:Temozolomide
keywords: DNA methylation; DNMT; DNMT inhibitor; GBM.; epigenetic; glioma