title: Survivin is a guardian of the intestinal stem cell niche and its expression is regulated by TGF-β.
abstract: 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-β 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.
authors.affiliation: a Department of Medicine 1 , Friedrich-Alexander-University , Erlangen , Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Martini
authors.affiliation: a Department of Medicine 1 , Friedrich-Alexander-University , Erlangen , Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Schneider
authors.affiliation: a Department of Medicine 1 , Friedrich-Alexander-University , Erlangen , Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Neufert
authors.affiliation: a Department of Medicine 1 , Friedrich-Alexander-University , Erlangen , Germany.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.affiliation: a Department of Medicine 1 , Friedrich-Alexander-University , Erlangen , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker
mesh_terms: D000818:Animals; D047108:Embryonic Development; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000166:cytology*; D008297:Male; D051379:Mice; D008938:Mitosis; D012097:Repressor Proteins / Q000378:metabolism*; D055153:Stem Cell Niche; D000077022:Survivin; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D016212:Transforming Growth Factor beta
keywords: BIRC5; colorectal cancer; inflammation; intestinal epithelium; mitotic catastrophe