EWS-FLI1 inhibits TNFα-induced NFκB-dependent transcription in Ewing sarcoma cells
| Autor: | Christian Auclair, Franck Tirode, Olivier Delattre, Alain Lilienbaum, Julie Lagirand-Cantaloube, Marie-Hélène Kryszke, Karine Laud |
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| Přispěvatelé: | Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Stress et pathologies du cytosquelette EA 300, Université Paris Diderot - Paris 7 (UPD7), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherches de biochimie macromoléculaire ( CRBM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR122-Centre National de la Recherche Scientifique ( CNRS ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) |
| Rok vydání: | 2010 |
| Předmět: |
Oncogene Proteins
Fusion Transcription Genetic Electrophoretic Mobility Shift Assay MESH : Oncogene Proteins Fusion medicine.disease_cause Biochemistry 0302 clinical medicine MESH: Transcription Factor RelA Genes Reporter Transcription (biology) Gene expression Luciferases MESH : Tumor Necrosis Factor-alpha 0303 health sciences Gene knockdown MESH: Proto-Oncogene Protein c-fli-1 MESH: Gene Expression Regulation Neoplastic MESH : Genes Reporter MESH: Bone Neoplasms Gene Expression Regulation Neoplastic MESH: Sarcoma Ewing's MESH : Sarcoma Ewing's MESH : Electrophoretic Mobility Shift Assay 030220 oncology & carcinogenesis Tumor necrosis factor alpha MESH: Cell Line Tumor MESH : Gene Expression Regulation Neoplastic Biophysics Bone Neoplasms Sarcoma Ewing Biology 03 medical and health sciences Cell Line Tumor medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology Transcription factor MESH : Bone Neoplasms 030304 developmental biology MESH : Luciferases MESH: Humans Proto-Oncogene Protein c-fli-1 Tumor Necrosis Factor-alpha MESH : Cell Line Tumor MESH: Transcription Genetic MESH : Transcription Factor RelA MESH : Humans MESH: Genes Reporter fungi Transcription Factor RelA MESH : Transcription Genetic Promoter Cell Biology Fusion protein MESH : Proto-Oncogene Protein c-fli-1 MESH: Tumor Necrosis Factor-alpha MESH: Electrophoretic Mobility Shift Assay Cancer research MESH: Luciferases RNA-Binding Protein EWS Carcinogenesis MESH: Oncogene Proteins Fusion |
| Zdroj: | Biochemical and Biophysical Research Communications Biochemical and Biophysical Research Communications, Elsevier, 2010, 399 (4), pp.705-10. ⟨10.1016/j.bbrc.2010.08.004⟩ Biochemical and Biophysical Research Communications, Elsevier, 2010, 399 (4), pp.705-10. 〈10.1016/j.bbrc.2010.08.004〉 |
| ISSN: | 0006-291X 1090-2104 |
| DOI: | 10.1016/j.bbrc.2010.08.004 |
| Popis: | International audience; Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1 acts as an aberrant transcription factor, broadly altering the gene expression profile of tumor cells. Nuclear factor-kappaB (NFkappaB) is a tightly regulated transcription factor controlling cell survival, proliferation and differentiation, as well as tumorigenesis. NFkappaB activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NFkappaB activity could be modulated by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells, we demonstrated that EWS-FLI1 has no influence on NFkappaB basal activity, but impairs TNF-induced NFkappaB-driven transcription, at least in part through inhibition of NFkappaB binding to DNA. We detected an in vivo physical interaction between the fusion protein and NFkappaB p65, which could mediate these effects. Our findings suggest that, besides directly controlling the activity of its primary target promoters, EWS-FLI1 can also indirectly influence gene expression in tumor cells by modulating the activity of key transcription factors such as NFkappaB. |
| Databáze: | OpenAIRE |
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