4.6 Article

Survivin is a guardian of the intestinal stem cell niche and its expression is regulated by TGF-

Journal

CELL CYCLE
Volume 15, Issue 21, Pages 2875-2881

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2016.1231286

Keywords

BIRC5; colorectal cancer; inflammation; intestinal epithelium; mitotic catastrophe

Categories

Funding

  1. DFG [FOR2438, SFB1181]
  2. DFG within clinical research unit KFO257
  3. Interdisciplinary Center for Clinical Research (IZKF) of the University Erlangen-Nurnberg
  4. European Community
  5. [SPP1656]
  6. [SFB796]
  7. [BE3686/2]

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As an inhibitor of apoptosis (IAP) family member, Survivin is known for its role during regulation of apoptosis. More recently its function as a cell cycle regulator has become evident. Survivin was shown to play a pivotal role during embryonic development and is highly expressed in regenerative tissue as well as in many cancer types. We examined the function of Survivin during mouse intestinal organogenesis and in gut pathophysiology. We found high expression of Survivin in experimentally induced colon cancer in mice but also in colon tumors of humans. Moreover, Survivin was regulated by TGF- and was found to be highly expressed during mucosal healing following intestinal inflammation. We identified that expression of Survivin is essential early on in life, as specific deletion of Survivin in Villin expressing cells led to embryonic death around day 12 post coitum. Together with our recent study on the role of Survivin in the gut of adult mice our data demonstrate that Survivin is an essential guardian of embryonic gut development and adult gut homeostasis protecting the epithelium from cell death promoting the proliferation of intestinal stem and progenitor cells.

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