Gastric cancer and Hedgehog signaling pathway: emerging new paradigms.

Adamu Ishaku Akyala,Maikel P. Peppelenbosch

doi:10.18632/genesandcancer.168

Adamu Ishaku Akyala, Maikel P. Peppelenbosch

Open Access

https://doi.org/10.18632/genesandcancer.168

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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.

Highlights

Hedgehog proteins are fundamental regulators of embryological development, and tissue homeostasis in adult organisms
The importance of Hedgehog signaling gastric pathophysiology has led to hopes that pharmacological inhibitors of this signaling may become useful for combating oncological disease in the stomach and this consideration prompted us to review here the detailed molecular mechanism by which Hedgehog influences gastric pathophysiology and to evaluate the evidence that anti-Hedgehog strategies will prove effective in this respect
A link exists through the immune system; several studies show that www.Genes&Cancer.com in gastritis the phenotype of infiltrating myeloid cells changes over time to become myeloid-derived suppressor cells (MDSCs) and that this phenotypic switch requires Hedgehog signaling

Summary

Introduction

Hedgehog proteins are fundamental regulators of embryological development, and tissue homeostasis in adult organisms. Both autocrine and www.Genes&Cancer.com paracrine Hedgehog signaling should be sensitive to pharmacological inhibitors and are tested in clinical trials in addition to an intense preclinical research effort[16]. NOTE: NA: not available; Hh: Hedgehog; Gli: glioma-associated oncogene; Ptch: Patched; Smo: Smoothened; Shh: Sonic Hh; IHC = immunohistochemistry, ISH= in situ hybridization, LacZ reporter.

Results

Conclusion