Gastric cancer and Hedgehog signaling pathway: emerging new paradigms
Adamu Ishaku Akyala1,2 and Maikel P. Peppelenbosch1
1 Department of Gastroenterology and Hepatology, Erasmus MC, Erasmus University, Rotterdam, Rotterdam, The Netherlands
2 Department of Microbiology, Faculty of Natural and Applied Sciences Nasarawa State University, Keffi, Nasarawa, Nigeria
Correspondence:
Adamu Ishaku Akyala, email:
Keywords: patched; receptors; smoothened receptor; zinc finger protein GLI1; precision medicine
Received: January 11, 2018 Accepted: March 25, 2018 Published: Apri 07, 2018
Abstract
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.
