Sonic hedgehog in gastric physiology and neoplastic transformation: Friend or foe?

Mohamad El-Zaatari, Milena Saqui-Salces, Megna Waghray, Andrea Todisco, Juanita L. Merchant

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)60-65
Number of pages6
JournalCurrent Opinion in Endocrinology, Diabetes and Obesity
Volume16
Issue number1
DOIs
StatePublished - Feb 2009

Keywords

  • Hypochlorhydria
  • Inflammation
  • Metaplasia
  • Paracrine
  • Stomach cancer

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