文章基本信息

标题：Epithelial Wnt secretion drives the progression of inflammation-induced colon carcinoma in murine model
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作者：Bahar Degirmenci ; Cansu Dincer ; Habibe Cansu Demirel 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：12
页码：1-14
DOI：10.1016/j.isci.2021.103369
语种：English
出版社：Elsevier
摘要：SummaryColon 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.Graphical abstractDisplay OmittedHighlights•Acquired expression of epithelial Wnts can drive colon cancer in murine AOM/DSS model•Blocking epithelial Wnt-secretion induces apoptosis of AOM/DSS cancer cells•The loss of epithelial Wnts promotes differentiation of Wnt-dependent colon tumors•Organoids derived from AOM/DSS cancer depend on self-autonomously secreted WntsMolecular physiology; Immunology; Cell biology; Cancer; Omics