| First Author | Colomer C | Year | 2018 |
| Journal | Br J Cancer | Volume | 118 |
| Issue | 6 | Pages | 839-846 |
| PubMed ID | 29438366 | Mgi Jnum | J:317021 |
| Mgi Id | MGI:6844541 | Doi | 10.1038/bjc.2017.459 |
| Citation | Colomer C, et al. (2018) IKKalpha is required in the intestinal epithelial cells for tumour stemness. Br J Cancer 118(6):839-846 |
| abstractText | 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-kappaB signalling is a key element in cancer, mainly related to the activity of IKKbeta. IKKalpha 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 IKKalpha, produced intestinal organoids and tumour spheroids with different genetic backgrounds, and performed immunohistochemistry and RNA-seq analysis. RESULTS: Deficiency of IKKalpha prevents adenoma formation, with adenomas lacking IKKalpha showing reduced proliferation. In contrast, IKKalpha status did not affect normal intestinal function. The same divergent phenotype was found in the organoid-spheroid model. We also found that epithelial IKKalpha controls stemness, proliferation and apoptosis-related expression. CONCLUSIONS: IKKalpha is a potential therapeutic target for Apc mutant colorectal cancer patients. |
