PURPOSE OF REVIEW: To understand the role of sonic hedgehog (Shh) in normal gastric physiology and neoplastic transformation. RECENT FINDINGS: Emerging evidence shows that gastric epithelial cells produce Shh ligand, which subsequently targets the mesenchyme. This paracrine signaling event is recapitulated by Shh-producing tumors that signal to the supporting stroma to encourage growth. Primary cilia contain components of the hedgehog signaling apparatus, and thus are typically found on responding stromal cells. SUMMARY: In the stomach, Shh is produced in epithelial cells and received by responding cells in the mesenchyme. In vitro, Shh enhances gastric acid secretion and induces mucin expression. It remains to be determined whether the canonical signaling pathway mediates the observed epithelial effects. Shh expression and signaling is reduced in chronic gastritis, and Shh(-/-) embryos exhibit hyperplasia and metaplastic changes in the gastric mucosa. After its loss in the corpus, Shh is re-expressed in some gastric carcinomas typically arising in the distal stomach or antrum, suggesting that it promotes tumor growth.
PURPOSE OF REVIEW: To understand the role of sonic hedgehog (Shh) in normal gastric physiology and neoplastic transformation. RECENT FINDINGS: Emerging evidence shows that gastric epithelial cells produce Shh ligand, which subsequently targets the mesenchyme. This paracrine signaling event is recapitulated by Shh-producing tumors that signal to the supporting stroma to encourage growth. Primary cilia contain components of the hedgehog signaling apparatus, and thus are typically found on responding stromal cells. SUMMARY: In the stomach, Shh is produced in epithelial cells and received by responding cells in the mesenchyme. In vitro, Shh enhances gastric acid secretion and induces mucin expression. It remains to be determined whether the canonical signaling pathway mediates the observed epithelial effects. Shh expression and signaling is reduced in chronic gastritis, and Shh(-/-) embryos exhibit hyperplasia and metaplastic changes in the gastric mucosa. After its loss in the corpus, Shh is re-expressed in some gastric carcinomas typically arising in the distal stomach or antrum, suggesting that it promotes tumor growth.
Authors: Robert L Yauch; Stephen E Gould; Suzie J Scales; Tracy Tang; Hua Tian; Christina P Ahn; Derek Marshall; Ling Fu; Thomas Januario; Dara Kallop; Michelle Nannini-Pepe; Karen Kotkow; James C Marsters; Lee L Rubin; Frederic J de Sauvage Journal: Nature Date: 2008-08-27 Impact factor: 49.962
Authors: Courtney J Haycraft; Tatiana Y Besschetnova; Pamela V Tran; Annick Turbe-Doan; Rolf W Stottmann; Bruce J Herron; Allyson L Chesebro; Haiyan Qiu; Paul J Scherz; Jagesh V Shah; Bradley K Yoder; David R Beier Journal: Nat Genet Date: 2008-03-09 Impact factor: 38.330
Authors: Mohamad El-Zaatari; Yana Zavros; Art Tessier; Meghna Waghray; Steve Lentz; Deborah Gumucio; Andrea Todisco; Juanita L Merchant Journal: Gastroenterology Date: 2010-10-20 Impact factor: 22.682
Authors: Steve S Choi; Wing-Kin Syn; Gamze F Karaca; Alessia Omenetti; Cynthia A Moylan; Rafal P Witek; Kolade M Agboola; Youngmi Jung; Gregory A Michelotti; Anna Mae Diehl Journal: J Biol Chem Date: 2010-09-14 Impact factor: 5.157