Wnt signaling and c-Myc in intestinal epithelium

Abstract

constantly produce cells from a stem cell reservoir that give rise to proliferating transit amplifying cells, which subsequently differentiate and are positioned in their proper compartments. This process has to be under stringent control to ensure life-long tissue homeostasis. It has now become clear that the same signaling pathways that are important during embryonic development control selfreneving tissues. Canonical Wnt signaling plays a key role in regulating intestinal tissue homeostasis. Moreover the same pathway is disregulated during intestinal tumorogenesis due to mutations of crucial pathway components. Over past years research has focused in revealing the molecular mechanism on how Wnt signaling regulates normal intestinal homeostasis and promotes cancer development. These studies revealed closely linked roles of Wnt signaling in homeostatic selfrenewal and cancer as genetic program induced in colorectal cancer cells is active in native intestinal progenitor cells. This program promotes proliferation and imposes intestinal progenitor cells to cancer phenotype, when ectopically active. The focus of the current research is to reveal the significance and contribution of the individual members in this genetic program of normal intestinal homeostasis and cancer. Here we briefly describe architecture of gastro-intestinal tract and Wnt signaling pathway components. We further summarise recent insights on how Wnt signaling controls intestinal epithelial homeostasis and cancer formation. We then discuss Wnt target genes from their perspective role in cancer formation. At the end we underline the potential importance of Wnt signaling in promoting various regenerative processes and introduce the significance of intestinal epithelial regeneration.