Guanylyl cyclase C signaling axis and colon cancer prevention

Figure 1 Guanylyl cyclase C receptor signaling, silencing, and reactivation. Ligand-mediated (guanylin and uroguanylin) activation of GUCY2C in the intestinal epithelial cell leads to accumulation of cGMP. This results in the maintenance of homeostatic mechanism, including regulated proliferation, barrier integrity, and proper cellular metabolism. Silencing of GUCY2C signaling by loss of hormone ligands leads to changes including increased glycolysis, increased proliferation, and a leaky intestinal barrier, all associated with colorectal tumorigenesis. These tumorigenic pathways potentially can be regulated with hormone replacement by oral supplementation with the analog linaclotide which restores GUCY2C signaling to re-establish homeostasis. GUCY2C: Guanylyl cyclase C; cGMP: Cyclic guanosine monophosphate.