Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach.
Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach.
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DOI：
10.4291/wjgp.v2.i6.103
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发表时间：
2011-12
期刊：
影响因子：
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通讯作者：
Alexander E. Sherman;Y. Zavros
中科院分区：
文献类型：
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作者：
Alexander E. Sherman;Y. Zavros
尽管治疗进展和发病率下降，胃癌仍然是世界上癌症相关死亡的第二大原因。了解胃从炎症到癌症的发展过程对于开发治疗这种疾病的新疗法和策略至关重要。胃的慢性炎症通常是由幽门螺杆菌（h.p ylori）引起的，由此引起的病变可能导致胃癌。在从炎症到癌症的发展过程中，胃上皮发生变化，正常上皮细胞分化被破坏，炎症细胞浸润。与萎缩性胃炎和化生的发展相一致的是胃形态因子Sonic Hedgehog （Shh）的丧失。鉴于其作为胃组织稳态调节剂的关键作用，炎症期间Shh表达的中断与正常上皮细胞分化的丧失相关，但直到最近才通过一种独特的靶向胃Shh缺失小鼠模型在体内进行了严格的测试。虽然萎缩性胃炎和肠化生等肿瘤前病变与胃泌酸腺中Shh的缺失有关，但Shh的升高与胃癌的信号传导之间存在明确的联系。目前的综述主要集中在Shh异常表达的影响及其在胃癌发展中的作用，特别是对幽门螺杆菌感染的反应。
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.