ArticleNeuro-oncology2016
An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells.
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Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Nucleases and Their Inhibitors: Exploring Biological Roles, Industrial Applications, and Challenges in Heterologous Expression.Biotechnology journal · 2026Review
- Evaluation of Pyrazolone-Based Hydrazones as Potential Therapeutic Agents Against Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2026Article
- A Mussel-Inspired Bioadhesive Patch to Selectively Kill Glioblastoma Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CAD hijacks STING to impair antitumor immunity and radiotherapy efficacy of colorectal cancer.Cell death & disease · 2025Article
- DNA fragmentation factor 40-based therapeutic approaches for cancer: a review article.Medical oncology (Northwood, London, England) · 2024Review
- Production of recombinant DNA fragmentation factor 40 in fusion to an antimicrobial peptide from spider venom and evaluation of its cytotoxic effects.Research in pharmaceutical sciences · 2024Article
- Temozolomide, Procarbazine and Nitrosoureas in the Therapy of Malignant Gliomas: Update of Mechanisms, Drug Resistance and Therapeutic Implications.Journal of clinical medicine · 2023Review
- Energetic metabolic reprogramming in Jurkat DFF40-deficient cancer cells.Molecular and cellular biochemistry · 2022Article
- The dual role of the CD95 and CD95L signaling pathway in glioblastoma.Frontiers in immunology · 2022Review
- Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells.Cancers · 2021Article
- DFF40-iRGD, a novel chimeric protein with efficient cytotoxic and apoptotic effects against triple-negative breast cancer cells.Biotechnology letters · 2021Article
- The role of the DFF40/CAD endonuclease in genomic stability.Apoptosis : an international journal on programmed cell death · 2021Review
- Two Simple Methods for Optimizing the Production of "Difficult-to-Express" GnRH-DFF40 Chimeric Protein.Advanced pharmaceutical bulletin · 2019Article
- PIM kinases mediate resistance of glioblastoma cells to TRAIL by a p62/SQSTM1-dependent mechanism.Cell death & disease · 2019Article
- Immunoexpression of DNA fragmentation factor 40, DNA fragmentation factor 45, and B-cell lymphoma 2 protein in normal human endometrium and uterine myometrium depends on menstrual cycle phase and menopausal status.Archives of medical science : AMS · 2018Article
- Autonomic nervous system and cancer.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2018Review
- DNA fragmentation factors 40 and 45 (DFF40/DFF45) and B-cell lymphoma 2 (Bcl-2) protein are underexpressed in uterine leiomyosarcomas and may predict survival.OncoTargets and therapy · 2017Article
- Reaching the point-of-no-return: The cornerstone of glioblastoma treatment?Neuro-oncology advancesReview
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Authors and funding
13 authors at 7 institutions in 1 country.
María Sánchez-OsunaCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Laura Martínez-EscardóCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Carla Granados-ColominaCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Fina Martínez-SolerCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Sònia Pascual-GuiralCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Victoria Iglesias-GuimaraisCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Roser VelascoCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Gerard PlansCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Noemi VidalCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Avelina TortosaCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Carlos BarciaCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Jordi BrunaCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Victor J YusteCell Death, Senescence and Survival group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (M.S.-O., L.M.-E., C.G.-C., S.P.-G., V.I.-G., V.J.Y.); Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (C.I.B.E.R.N.E.D.), Barcelona, Spain (M.S.-O., V.I.-G., V.J.Y.); Department of Basic Nursing, Institut d'Investigació Biomèdica de Bellvitge-Universitat de Barcelona, Barcelona, Spain (F.M.-S., A.T.); Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-I.C.O Duran i Reynals, Barcelona, Spain (R.V., G.P., N.V., J.B.); Group of Neuroplasticity and Regeneration (C.I.B.E.R.N.E.D.), Department of Cell Biology, Physiology and Immunology & Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain (R.V., J.B.); Neuropathology Institute, Hospital Universitari de Bellvitge, Barcelona, Spain (N.V.); Neuro-Immunity Group, Department of Biochemistry and Molecular Biology and Institute of Neurosciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (C.B.).
Institut d'Investigació Biomédica de Bellvitge · ESBellvitge University Hospital · ESBiomedical Research Networking Center on Neurodegenerative Diseases · ESCentro de Investigación Biomédica en Red · ESDuran i Reynals Hospital · ESUniversitat Autònoma de Barcelona · ESUniversitat de Barcelona · ES
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma (GBM) or grade IV astrocytoma is one of the most devastating human cancers. The loss of DFF40/CAD, the key endonuclease that triggers oligonucleosomal DNA fragmentation during apoptosis, has been linked to genomic instability and cell survival after radiation. Despite the near inevitability of GBM tumor recurrence after treatment, the relationship between DFF40/CAD and GBM remains unexplored.
methodsWe studied the apoptotic behavior of human GBM-derived cells after apoptotic insult. We analyzed caspase activation and the protein levels and subcellular localization of DFF40/CAD apoptotic endonuclease. DFF40/CAD was also evaluated in histological sections from astrocytic tumors and nontumoral human brain.
resultsWe showed that GBM cells undergo incomplete apoptosis without generating oligonucleosomal DNA degradation despite the correct activation of executioner caspases. The major defect of GBM cells relied on the improper accumulation of DFF40/CAD at the nucleoplasmic subcellular compartment. Supporting this finding, DFF40/CAD overexpression allowed GBM cells to display oligonucleosomal DNA degradation after apoptotic challenge. Moreover, the analysis of histological slices from astrocytic tumors showed that DFF40/CAD immunoreactivity in tumoral GFAP-positive cells was markedly reduced when compared with nontumoral samples.
conclusionsOur data highlight the low expression levels of DFF40/CAD and the absence of DNA laddering as common molecular traits in GBM. These findings could be of major importance for understanding the malignant behavior of remaining tumor cells after radiochemotherapy.
Indexed as
ApoptosisApoptosis Regulatory ProteinsCaspasesCell Line, TumorDeoxyribonucleasesDNAExoribonucleasesGlioblastomaHumansPoly-ADP-Ribose Binding ProteinsApoptosis Regulatory ProteinsCaspasesDeoxyribonucleasesDFFB protein, humanDNAExoribonucleasesoligonucleotidasePoly-ADP-Ribose Binding Proteinsapoptosiscaspase-dependent cell deathcaspase-dependent DNase (DFF40/CAD)glioblastomaoligonucleosomal DNA degradation
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