Histology of Paneth cells (by Mikael Häggström via Wikimedia Commons)

Many colorectal tumors originate from multipotent intestinal stem cells (ISCs), but some are thought to arise from de-differentiation of mature cells. Verhagen et al. have now demonstrated this process in secretory small intestinal cells known as Paneth cells. After inducing inflammation in mouse models bearing tissue-specific tumor suppressor mutations, they observed Paneth cells de-differentiating and forming tumors with distinct gene expression profiles relative to ISC-derived tumors. Under normal conditions, Paneth cells are absent in the colon, but these gene expression patterns closely resembled those observed in a sizable subset of colorectal cancer patients. The authors propose that a similar mechanism plays out in colorectal secretory cell types in response to cancer-promoting factors such as inflammatory bowel disease or consumption of high-fat Western diets, revealing a novel route for the onset—and potential prevention—of colorectal cancer.

Verhagen MP, … Fodde R. Nat...

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