Brg1 Loss Attenuates Aberrant Wnt-Signalling and Prevents Wnt-Dependent Tumourigenesis in the Murine Small Intestine

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Aberrant Wnt signalling is responsible for the majority of colorectal cancers, the third leading cause of cancer-related mortality in the UK. However, no therapies directly targeting Wnt signalling are currently available. Using mouse models of intestinal cancer, we demonstrate that deleting chromatin remodelling factor Brg1 in the context of Apc-deficient small intestinal epithelium attenuates Wnt-driven gene expression changes and prevents adenoma formation, which results in extended animal survival. We also demonstrate that Brg1 loss impairs the small intestinal stem cell expansion associated with aberrant activation of Wnt signalling. These findings highlight Brg1 as a potential therapeutic target in Wnt-driven intestinal tumourigenesis and illustrate the viability of targeting the somatic stem cell as the ‘cell of origin’ of cancer, which might be particularly valuable in patients with known predisposition to cancer.

Vyšlo v časopise: Brg1 Loss Attenuates Aberrant Wnt-Signalling and Prevents Wnt-Dependent Tumourigenesis in the Murine Small Intestine. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004453
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004453

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