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Noxa the BCL-2 Family Member behind the Scenes in Cancer Treatment

Alison Dumont 1 Steven Lohard 1 Laurent Maillet 1 Philippe Juin 1 Sophie Barillé-Nion 1
1 CRCINA-ÉQUIPE 8 - Stress Adaptation and Tumor Escape in Breast Cancer
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
Abstract : NOXA is a critical mediator of stress responses to anticancer drugs. This BH3-only protein sets the apoptotic threshold in cancer cells in response to chemotherapies by counteracting the prosurvival BCL-2 family protein MCL-1. A complex and dynamic network relying on both highly controlled gene transcription activity and protein degradation by proteasome, regulates cellular NOXA levels from low in steady state to rapidly enhanced upon stressful condition. Antimitotics and proteasome inhibitors are powerful anticancer treatments that mainly rely on NOXA activity to trigger death in cancer cells. In addition, in case of antimitotics, a wave of cell death based on NOXA and fueled by an automomous secretome spreads through the tumor, revealing new therapeutic opportunities. By neutralizing MCL-1 prosurvival activity, NOXA induces preferential BCL-2 or BCL-xL cancer cell survival dependencies, that can be exploited therapeutically using BH3 mimetics. Since MCL-1 interfers with tumor response to chemotherapies, promoting NOXA expression or using recently available MCL-1 targeting BH3 mimetics are promising opportunities to improve cancer treatments.
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https://www.hal.inserm.fr/inserm-03171678
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Submitted on : Wednesday, March 17, 2021 - 10:16:03 AM
Last modification on : Wednesday, October 20, 2021 - 3:19:38 AM
Long-term archiving on: : Monday, June 21, 2021 - 8:52:03 AM

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Alison Dumont, Steven Lohard, Laurent Maillet, Philippe Juin, Sophie Barillé-Nion. Noxa the BCL-2 Family Member behind the Scenes in Cancer Treatment. Journal of Cellular Signaling, Scientific Archives, 2020, 1 (4), pp.127. ⟨inserm-03171678⟩

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