Noxa the BCL-2 Family Member behind the Scenes in Cancer Treatment - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Cellular Signaling Year : 2020

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

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.

Domains

Cancer
Fichier principal
Vignette du fichier
JCS-20-021Eq8.pdf (860.92 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

inserm-03171678 , version 1 (17-03-2021)

Identifiers

  • HAL Id : inserm-03171678 , version 1

Cite

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

Share

Gmail Facebook X LinkedIn More