| First Author | van der Heijden M | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10916 | PubMed ID | 26956214 |
| Mgi Jnum | J:236502 | Mgi Id | MGI:5806213 |
| Doi | 10.1038/ncomms10916 | Citation | van der Heijden M, et al. (2016) Bcl-2 is a critical mediator of intestinal transformation. Nat Commun 7:10916 |
| abstractText | Intestinal tumour formation is generally thought to occur following mutational events in the stem cell pool. However, active NF-kappaB signalling additionally facilitates malignant transformation of differentiated cells. We hypothesized that genes shared between NF-kappaB and intestinal stem cell (ISCs) signatures might identify common pathways that are required for malignant growth. Here, we find that the NF-kappaB target Bcl-2, an anti-apoptotic gene, is specifically expressed in ISCs in both mice and humans. Bcl-2 is dispensable in homeostasis and, although involved in protecting ISCs from radiation-induced damage, it is non-essential in tissue regeneration. Bcl-2 is upregulated in adenomas, and its loss or inhibition impairs outgrowth of oncogenic clones, because Bcl-2 alleviates apoptotic priming in epithelial cells following Apc loss. Furthermore, Bcl-2 expression in differentiated epithelial cells renders these cells amenable to clonogenic outgrowth. Collectively, our results indicate that Bcl-2 is required for efficient intestinal transformation following Apc-loss and constitutes a potential chemoprevention target. |
