Sonic hedgehog in gastric physiology and neoplastic transformation: friend or foe?
OBJECTIVE
To understand the role of sonic hedgehog (Shh) in normal gastric physiology and neoplastic transformation.


RESULTS
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.


CONCLUSIONS
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.
El-Zaatari
Mohamad
M
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48198-2200, USA.
Saqui-Salces
Milena
M
Waghray
Megna
M
Todisco
Andrea
A
Merchant
Juanita L
JL
D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D023421:Models, Animal; D009077:Mucins / Q000235:genetics; D015398:Signal Transduction; D013270:Stomach / Q000502:physiology* / Q000503:physiopathology*; D013272:Stomach Diseases / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000503:physiopathology*
D053823:Hedgehog Proteins; D009077:Mucins; C509239:SHH protein, human