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. 2012 Apr 1;4(4):a007989.
doi: 10.1101/cshperspect.a007989.

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

Arnout Schepers  1 , Hans Clevers
Affiliations

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

Arnout Schepers et al. Cold Spring Harb Perspect Biol. .

Abstract

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.

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Figures

Figure 1.
Figure 1.
Anatomy of the human and mouse stomach. (A) Human stomach. (B) Mouse stomach. (C) Gastric unit of the pyloric antrum. (D) Gastric unit of the corpus.
Figure 2.
Figure 2.
Lgr5-positive CBC cells give rise to all epithelial lineages. (A) Low dose of tamoxifen activates Cre recombinase sporadically in CBC cells. (B) Multiple daughter cells are labeled 2 days after induction. (C) Induced Lgr5-positive cells generate labeled “ribbons” containing all different cell types of the intestinal epithelium for the lifetime of the mouse. (D) Architecture of a small intestinal crypt with the Wnt gradient depicted in red. (E) Schematic overview of the generation of different cell lineages from Lgr5+ve CBC stem cells.
Figure 3.
Figure 3.
Schematic representation of the Wnt signaling complex. (A) The classical complex comprised of Wnt, Frizzled, and low-density lipoprotein receptor-related protein (LRP). (B) New proposed model including the Lgr receptor and R-spondin.
See this image and copyright information in PMC

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