IKK-alpha is required in the intestinal epithelial cells for tumour stemness
Menée in vitro et à l'aide d'un modèle murin avec mutation du gène Apc et absence de la protéine IKK-alpha dans les cellules épithéliales de l'intestin, cette étude montre que cette protéine est nécessaire au développement des cellules tumorales
Background : Colorectal cancer is a common cause of death in developed countries. Progression from adenoma to invasive carcinoma requires accumulation of mutations starting with the Adenomatous Polyposis Coli (Apc) gene. NF-
κB signalling is a key element in cancer, mainly related to the activity of IKKβ. IKKα kinase also participates in this process by mechanisms that are primarily unknown. Methods
:
We generated a compound mouse model with mutation in Apc and lacking intestinal epithelial IKKα, produced intestinal organoids and tumour spheroids with different genetic backgrounds, and performed immunohistochemistry and RNA-seq analysis. Results
:
Deficiency of IKKα prevents adenoma formation, with adenomas lacking IKKα showing reduced proliferation. In contrast, IKKα status did not affect normal intestinal function. The same divergent phenotype was found in the organoid
–spheroid model. We also found that epithelial IKK
α controls stemness, proliferation and apoptosis-related expression. Conclusions
:
IKKα is a potential therapeutic target for Apc mutant colorectal cancer patients.