Cibler la survie des cellules souches cancéreuses dans le cancer du sein triple négatif grâce à l’inhibition de NF-κB par des effecteurs bactériens
DOI :
https://doi.org/10.18192/osurj.v5i2.8053Résumé
Le cancer du sein triple négatif est une forme agressive de cancer du sein. Il se caractérise par l’absence des récepteurs aux œstrogènes, à la progestérone et à HER2, ce qui limite l’efficacité de plusieurs traitements habituellement utilisés contre le cancer du sein. Dans ce contexte, la chimiothérapie demeure le traitement principal. Elle peut d’abord réduire la taille de la tumeur, mais le cancer triple négatif revient souvent après le traitement.
Cette récidive est en grande partie liée à la présence de cellules souches cancéreuses. Ces cellules représentent une petite population de cellules tumorales capables de se renouveler, de reformer une tumeur et de résister aux traitements. Un facteur important qui favorise leur survie est NF-κB, une protéine régulatrice qui contrôle l’expression de plusieurs gènes liés à l’inflammation, à la survie cellulaire et à la résistance au stress causé par les traitements. Dans le cancer du sein triple négatif, la voie NF-κB est souvent activée de façon constante, ce qui renforce la résistance des cellules souches cancéreuses à la chimiothérapie et augmente le risque de rechute.
Les traitements actuels ne permettent pas d’éliminer efficacement ces cellules souches cancéreuses ni de bloquer directement la voie NF-κB. Cela représente donc une limite importante dans la prise en charge de ce type de cancer. Cette étude vise à déterminer si certaines protéines effectrices bactériennes peuvent être réutilisées comme outils moléculaires ciblés pour inhiber la signalisation NF-κB dans le cancer du sein triple négatif. Ces protéines ont été choisies parce qu’elles sont capables de perturber l’activation de NF-κB.
Pour tester cette approche, des modèles de cancer du sein triple négatif ont été modifiés afin de permettre l’expression contrôlée de ces protéines effectrices dans différentes lignées cellulaires. L’activité de NF-κB a ensuite été évaluée par RT-qPCR et par cytométrie en flux. La cytométrie en flux a aussi été utilisée pour mesurer l’apoptose, c’est-à-dire la mort cellulaire programmée, ainsi que l’expression de marqueurs associés aux cellules souches cancéreuses.
Dans l’ensemble, ce travail permet de mieux comprendre comment cibler les mécanismes qui rendent les cellules souches cancéreuses résistantes aux traitements. Il pourrait aussi contribuer au développement de stratégies thérapeutiques plus précises pour traiter les formes agressives du cancer du sein triple négatif.
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