%0 Journal Article %T NF-κB Activation Represses Tumor Necrosis Factor-α-induced Autophagy %+ Signalisation et physiopathologie des cellules épithéliales %+ Università degli Studi di Milano = University of Milan (UNIMI) %+ Plasticite Phenotypique de la Cellule Tumorale : Signalisations, Mecanismes et Implications Therapeutiques %+ Hopital Saint-Louis [AP-HP] (AP-HP) %+ Génétique moléculaire et intégration des fonctions cellulaires (GMIFC) %A Djavaheri-Mergny, Mojgan %A Amelotti, Manuela %A Mathieu, Julie %A Besançon, Françoise %A Bauvy, Chantal %A Souquère, Sylvie %A Pierron, Gérard %A Codogno, Patrice %< avec comité de lecture %@ 0021-9258 %J Journal of Biological Chemistry %I American Society for Biochemistry and Molecular Biology %V 281 %N 41 %P 30373-30382 %8 2006-10 %D 2006 %R 10.1074/jbc.M602097200 %M 16857678 %Z Life Sciences [q-bio]Journal articles %X Activation of NF-kappaB and autophagy are two processes involved in the regulation of cell death, but the possible cross-talk between these two signaling pathways is largely unknown. Here, we show that NF-kappaB activation mediates repression of autophagy in tumor necrosis factor-alpha (TNFalpha)-treated Ewing sarcoma cells. This repression is associated with an NF-kappaB-dependent activation of the autophagy inhibitor mTOR. In contrast, in cells lacking NF-kappaB activation, TNFalpha treatment up-regulates the expression of the autophagy-promoting protein Beclin 1 and subsequently induces the accumulation of autophagic vacuoles. Both of these responses are dependent on reactive oxygen species (ROS) production and can be mimicked in NF-kappaB-competent cells by the addition of H2O2. Small interfering RNA-mediated knockdown of beclin 1 and atg7 expression, two autophagy-related genes, reduced TNFalpha- and reactive oxygen species-induced apoptosis in cells lacking NF-kappaB activation and in NF-kappaB-competent cells, respectively. These findings demonstrate that autophagy may amplify apoptosis when associated with a death signaling pathway. They are also evidence that inhibition of autophagy is a novel mechanism of the antiapoptotic function of NF-kappaB activation. We suggest that stimulation of autophagy may be a potential way bypassing the resistance of cancer cells to anti-cancer agents that activate NF-kappaB. %G English %2 https://inserm.hal.science/inserm-03653085/document %2 https://inserm.hal.science/inserm-03653085/file/PIIS0021925819892499.pdf %L inserm-03653085 %U https://inserm.hal.science/inserm-03653085 %~ INSERM %~ UNIV-PARIS7 %~ CNRS %~ UNIV-PSUD %~ APHP %~ UNIV-PARIS-SACLAY %~ UNIV-PSUD-SACLAY %~ UNIV-PARIS