Your browser doesn't support javascript.
loading
DNA damage repair kinase DNA-PK and cGAS synergize to induce cancer-related inflammation in glioblastoma.
Taffoni, Clara; Marines, Johanna; Chamma, Hanane; Guha, Soumyabrata; Saccas, Mathilde; Bouzid, Amel; Valadao, Ana-Luiza Chaves; Maghe, Clément; Jardine, Jane; Park, Mi Kyung; Polak, Katarzyna; De Martino, Mara; Vanpouille-Box, Claire; Del Rio, Maguy; Gongora, Celine; Gavard, Julie; Bidère, Nicolas; Song, Min Sup; Pineau, Donovan; Hugnot, Jean-Philippe; Kissa, Karima; Fontenille, Laura; Blanchet, Fabien P; Vila, Isabelle K; Laguette, Nadine.
Afiliação
  • Taffoni C; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Marines J; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Chamma H; Azelead©, Montpellier, France.
  • Guha S; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Saccas M; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Bouzid A; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Valadao AC; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Maghe C; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Jardine J; Team SOAP, CRCI2NA, Nantes Université, Inserm, CNRS, Université d'Angers, Nantes, France.
  • Park MK; Equipe Labellisée Ligue Contre le Cancer, Paris, France.
  • Polak K; Team SOAP, CRCI2NA, Nantes Université, Inserm, CNRS, Université d'Angers, Nantes, France.
  • De Martino M; Equipe Labellisée Ligue Contre le Cancer, Paris, France.
  • Vanpouille-Box C; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Del Rio M; IGH, Université de Montpellier, CNRS, Montpellier, France.
  • Gongora C; Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.
  • Gavard J; Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.
  • Bidère N; Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM, Université de Montpellier, ICM, Montpellier, France.
  • Song MS; Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM, Université de Montpellier, ICM, Montpellier, France.
  • Pineau D; Team SOAP, CRCI2NA, Nantes Université, Inserm, CNRS, Université d'Angers, Nantes, France.
  • Hugnot JP; Equipe Labellisée Ligue Contre le Cancer, Paris, France.
  • Kissa K; Institut de Cancérologie de l'Ouest (ICO), Saint-Herblain, France.
  • Fontenille L; Team SOAP, CRCI2NA, Nantes Université, Inserm, CNRS, Université d'Angers, Nantes, France.
  • Blanchet FP; Equipe Labellisée Ligue Contre le Cancer, Paris, France.
  • Vila IK; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Laguette N; Institut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERM, Montpellier, France.
EMBO J ; 42(7): e111961, 2023 04 03.
Article em En | MEDLINE | ID: mdl-36574362
Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment in a glioblastoma model, a process that impairs early tumorigenesis but correlates with poor outcome in glioblastoma patients. Thus, our study supports that cGAS-dependent signaling is acquired during tumorigenesis and that cGAS and DNA-PK activities should be analyzed concertedly to predict the impact of strategies aiming to boost tumor immunogenicity.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glioblastoma / Proteína Quinase Ativada por DNA / Nucleotidiltransferases Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glioblastoma / Proteína Quinase Ativada por DNA / Nucleotidiltransferases Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article