Without Apc or with a damaged version of this gene, Wnt signaling, which drives crypts regeneration, goes uncontrolled leading to tumor formation.
Researchers found that if a gene called Apc is lost or damaged, then its normal function of controlling the adult stem cell population breaks down and ultimately leads to a tumor.
The team manipulated intestinal stem cells and mimiced the process by which a part of the intestine called the crypts is regenerated following high levels of DNA damage or injury. By doing this, they observed that Wnt signaling drives this process and is necessary to convert stem cells to replacement cells in the damaged part of the intestine.
The investigators also showed that Apc has a role in switching off Wnt signaling. Under normal circumstances, Wnt signaling is turned down once the stem cells have done their job. If Apc is lost or damaged, this does not happen and an increased number of cells are added to the crypt, and ultimately a tumor forms, report the scientists.
The research was conducted by Alan Clarke, Ph.D., professor at Cardiff University and Owen Sansom, Ph.D., from the University of Glasgow. Dr. Clarke presented the results on April 10 at the “UK National Stem Cell Network Annual Science Meeting.”