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World J Gastrointest Pathophysiol. Dec 15, 2011; 2(6): 103-108
Published online Dec 15, 2011. doi: 10.4291/wjgp.v2.i6.103
Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach
Alexander E Sherman, Yana Zavros
Alexander E Sherman, Yana Zavros, Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0576, United States
Author contributions: Sherman AE drafted the manuscript; Sherman AE and Zavros Y critically revised the manuscript for important intellectual content; Zavros Y obtained funding and performed the study supervision.
Supported by American Cancer Society Research Scholar Award, No. 119072-RSG-10-167-01-MPC (to Zavros Y)
Correspondence to: Yana Zavros, PhD, Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, MSB Room 1113, Cincinnati, OH 45267-0576, United States. yana.zavros@uc.edu
Telephone: +1-513-5582421 Fax: +1-513-5585736
Received: August 1, 2011
Revised: September 20, 2011
Accepted: October 14, 2011
Published online: December 15, 2011
Abstract

Despite advances in treatment and the declining incidence, gastric cancer remains the second leading cause of cancer-related deaths in the world. Understanding the progression from inflammation to cancer in the stomach is crucial in the development of novel therapies and strategies for treating this disease. Chronic inflammation of the stomach is typically caused by Helicobacter pylori (H. pylori) and resulting lesions may lead to gastric cancer. During the progression from inflammation to cancer, the stomach epithelium changes with evidence of the disruption of normal epithelial cell differentiation and infiltrating inflammatory cells. Coincident with the development of atrophic gastritis and metaplasia, is the loss of the gastric morphogen Sonic Hedgehog (Shh). Given its critical role as a regulator of gastric tissue homeostasis, the disruption of Shh expression during inflammation correlates with the loss of normal epithelial cell differentiation, but this has only recently been rigorously tested in vivo using a unique mouse model of targeted gastric Shh deletion. While pre-neoplastic lesions such as atrophic gastritis and intestinal metaplasia are associated with the loss of Shh within the acid-secreting glands of the stomach, there is a clear link between elevated Shh and signaling to gastric cancers. The current review focuses on the effects of aberrant Shh expression and its role in the development of gastric cancer, specifically in response to H. pylori infection.

Keywords: Helicobacter pylori; Interleukin-1β; Acid secretion; Gastric tissue homeostasis