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Publication : Epithelial Wnt secretion drives the progression of inflammation-induced colon carcinoma in murine model.

First Author  Degirmenci B Year  2021
Journal  iScience Volume  24
Issue  12 Pages  103369
PubMed ID  34849464 Mgi Jnum  J:316092
Mgi Id  MGI:6833972 Doi  10.1016/j.isci.2021.103369
Citation  Degirmenci B, et al. (2021) Epithelial Wnt secretion drives the progression of inflammation-induced colon carcinoma in murine model. iScience 24(12):103369
abstractText  Colon cancer is initiated by stem cells that escape the strict control. This process is often driven through aberrant activation of Wnt signaling by mutations in components acting downstream of the receptor complex that unfetter tumor cells from the need for Wnts. Here we describe a class of colon cancer that does not depend on mutated core components of the Wnt pathway. Genetically blocking Wnt secretion from epithelial cells of such tumors results in apoptosis, reduced expression of colon cancer markers, followed by enhanced tumor differentiation. In contrast to the normal colonic epithelium, such tumor cells autosecrete Wnts to maintain their uncontrolled proliferative behavior. In humans, we determined certain cases of colon cancers in which the Wnt pathway is hyperactive, but not through mutations in its core components. Our findings illuminate the path in therapy to find further subtypes of Wnt-dependent colon cancer that might be responsive to Wnt secretion inhibitors.
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