Gastric cancer and Hedgehog signaling pathway: emerging new paradigms.
Gastric cancer and Hedgehog signaling pathway: emerging new paradigms.
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DOI：
10.18632/genesandcancer.168
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Peppelenbosch MP
中科院分区：
文献类型：
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作者：
Akyala AI;Peppelenbosch MP
自从在果蝇中首次发现以来，刺猬信号一直与前肠发育有关，哺乳动物基因组表达三种刺猬旁系同源物，音刺猬（Shh），印度刺猬和沙漠刺猬。在胚胎和成体前肠粘膜中，Shh表达最高。现在已经清楚的是，刺猬信号在胃内稳态中具有关键的重要性。刺猬信号的异常激活与包括各种癌症在内的一系列病理后果有关。同样在胃癌中，临床和临床前数据支持Hedgehog信号传导在肿瘤转化和胃肠道癌症发展中的作用，也通过癌症基质相互作用。技术进步促进了Hedgehog信号的监测，拓宽了更有效地筛选最终易患胃癌的个体的选择，并且一旦萎缩性胃炎发生，靶向Hedgehog信号可能为预防性治疗提供机会。然而，Hedgehog拮抗剂在胃癌的背景下具有临床有用性的令人信服的证据仍然明显缺乏。本文就Hedgehog在胃生理学中的作用以及Hedgehog信号通路在胃癌中的应用进行综述。
Ever since its initial discovery in Drosophila, hedgehog signaling has been linked to foregut development, The mammalian genome expresses three Hedgehog paralogues, sonic hedgehog (Shh), Indian Hedgehog, and desert hedgehog. In the mucosa of the embryonic and adult foregut, Shh expression is the highest. It has now become clear that hedgehog signaling is of pivotal importance in gastric homeostasis. Aberrant activation of hedgehog signaling is associated with a range of pathological consequences including various cancers. Also in gastric cancer, clinical and preclinical data support a role of Hedgehog signaling in neoplastic transformation, and gastrointestinal cancer development, also through cancer stroma interaction. Technological advance are facilitating monitoring Hedgehog signaling broadening options for the more efficient screening of individuals predisposed to eventually developing gastric cancer and targeting Hedgehog signaling may provide opportunities for prophylactic therapy once atrophic gastritis develops. Nevertheless, convincing evidence that Hedgehog antagonists are of clinically useful in the context of gastric cancer is still conspicuously lacking. Here we analyze review the role of Hedgehog in gastric physiology and the potential usefulness of targeting Hedgehog signaling in gastric cancer.