Ikk Alpha Is Required In The Intestinal Epithelial Cells For Tumour Stemness

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-kappa B signalling is a key element in cancer, mainly related to the activity of IKK beta. IKK alpha 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 IKK alpha, produced intestinal organoids and tumour spheroids with different genetic backgrounds, and performed immunohistochemistry and RNA-seq analysis.Results: Deficiency of IKK alpha prevents adenoma formation, with adenomas lacking IKK alpha showing reduced proliferation. In contrast, IKK alpha status did not affect normal intestinal function. The same divergent phenotype was found in the organoid-spheroid model. We also found that epithelial IKK alpha controls stemness, proliferation and apoptosis-related expression.Conclusions: IKK alpha is a potential therapeutic target for Apc mutant colorectal cancer patients.