4.8 Article

Apc-mutant cells act as supercompetitors in intestinal tumour initiation

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NOTUM from Apc-mutant cells biases clonal competition to initiate cancer

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Summary: The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling, while reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt. The study found that Apc-mutant cells are enriched for transcripts encoding several secreted WNT antagonists, with Notum being the most highly expressed. These cells actively inhibit the proliferation of surrounding wild-type crypt cells, outcompeting them in the niche and driving their differentiation.

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