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TCTP regulates genotoxic stress and tumorigenicity via intercellular vesicular signaling.
Amson, Robert; Senff-Ribeiro, Andrea; Karafin, Teele; Lespagnol, Alexandra; Honoré, Joane; Baylot, Virginie; Banroques, Josette; Tanner, N Kyle; Chamond, Nathalie; Dimitrov, Jordan D; Hoebeke, Johan; Droin, Nathalie M; Job, Bastien; Piard, Jonathan; Bommer, Ulrich-Axel; Choi, Kwang-Wook; Abdelfatah, Sara; Efferth, Thomas; Telerman, Stephanie B; Geyer, Felipe Correa; Reis-Filho, Jorge; Telerman, Adam.
Afiliação
  • Amson R; Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Senff-Ribeiro A; Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Karafin T; Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Lespagnol A; Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Honoré J; Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Baylot V; Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Banroques J; Université de Paris Cité & CNRS, Expression Génétique Microbienne, IBPC, 13 rue Pierre et Marie Curie and Institut de Biologie Physico-Chimique, Paris Sciences et Lettres University, CNRS UMR8261, EGM, 75005, Paris, France.
  • Tanner NK; Université de Paris Cité & CNRS, Expression Génétique Microbienne, IBPC, 13 rue Pierre et Marie Curie and Institut de Biologie Physico-Chimique, Paris Sciences et Lettres University, CNRS UMR8261, EGM, 75005, Paris, France.
  • Chamond N; Faculté de Pharmacie de Paris, Laboratoire CiTCom - UMR CNRS 8038 Université Paris Descartes 4 Avenue de l'Observatoire, 75270, Paris, France.
  • Dimitrov JD; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, Université de Paris, 75006, Paris, France.
  • Hoebeke J; Institut de Biologie Moléculaire et Cellulaire, UPR CNRS 9021, 15, rue René Descartes, 67084, Strasbourg, France.
  • Droin NM; Institut Gustave Roussy (IGR), Unité Inserm U1287, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Job B; Institut Gustave Roussy (IGR), Bioinformatics Core Facility, 114 rue Édouard-Vaillant, 94805, Villejuif, France.
  • Piard J; Département de Chimie, Ecole Normale Supérieure Paris-Saclay, 4 avenue Des Sciences, 91110, Gif-sur-Yvette, France.
  • Bommer UA; Graduate School of Medicine, Faculty of Science, Medicine & Health, University of Wollongong, Wollongong, NSW, 2522, Australia.
  • Choi KW; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Korea.
  • Abdelfatah S; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Science, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
  • Efferth T; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Science, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
  • Telerman SB; Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
  • Geyer FC; Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Ave, New York, NY, 10065, USA.
  • Reis-Filho J; Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Ave, New York, NY, 10065, USA.
  • Telerman A; Institut Gustave Roussy (IGR), Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805, Villejuif, France. atelerman@gmail.com.
EMBO Rep ; 25(4): 1962-1986, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38548973
ABSTRACT
Oncogenic intercellular signaling is regulated by extracellular vesicles (EVs), but the underlying mechanisms remain mostly unclear. Since TCTP (translationally controlled tumor protein) is an EV component, we investigated whether it has a role in genotoxic stress signaling and malignant transformation. By generating a Tctp-inducible knockout mouse model (Tctp-/f-), we report that Tctp is required for genotoxic stress-induced apoptosis signaling via small EVs (sEVs). Human breast cancer cells knocked-down for TCTP show impaired spontaneous EV secretion, thereby reducing sEV-dependent malignant growth. Since Trp53-/- mice are prone to tumor formation, we derived tumor cells from Trp53-/-;Tctp-/f- double mutant mice and describe a drastic decrease in tumori-genicity with concomitant decrease in sEV secretion and content. Remarkably, Trp53-/-;Tctp-/f- mice show highly prolonged survival. Treatment of Trp53-/- mice with sertraline, which inhibits TCTP function, increases their survival. Mechanistically, TCTP binds DDX3, recruiting RNAs, including miRNAs, to sEVs. Our findings establish TCTP as an essential protagonist in the regulation of sEV-signaling in the context of apoptosis and tumorigenicity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Neoplasias Limite: Animals / Humans Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Neoplasias Limite: Animals / Humans Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França