IKK α 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- κ B signalling is a key element in cancer, mainly related to the activity of IKK β . IKK α 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 α , produced intestinal organoids and tumour spheroids with different genetic backgrounds, and performed immunohistochemistry and RNA-seq analysis. Results: Deficiency of IKK α prevents adenoma formation, with adenomas lacking IKK α showing reduced proliferation. In contrast, IKK α 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: IKK α is a potential therapeutic target for Apc mutant colorectal cancer patients.