Wnt signaling, stem cells, and cancer of the gastrointestinal tract.

The Wnt signaling pathway was originally uncovered as one of the prototype developmental signaling cascades in invertebrates as well as in vertebrates. The first indication that Wnt signaling also plays a role in the adult animal came from the study of the intestine of Tcf-4 (Tcf7L2) knockout mice. The gastrointestinal epithelium continuously self-renews over the lifetime of an organism and is, in fact, the most rapidly self-renewing tissue of the mammalian body. Recent studies indicate that Wnt signaling plays a central role in the biology of gastrointestinal stem cells. Furthermore, mutational activation of the Wnt cascade is the principle cause of colon cancer.