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The Role of Sonic Hedgehog Reemergence During Gastric Cancer

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Abstract

Sonic Hedgehog (Shh) signaling has been extensively studied for its role in developmental biology and cancer biology. The association between Shh and cancer development in general is well established but the functional role of Shh in the development and progression of gastric cancer specifically is largely unknown. Bone marrow-derived stem cells, specifically mesenchymal stem cells (MSCs) infiltrate and engraft into the gastric mucosa in response to the chronic inflammatory environment of Helicobacter infection. In this review, MSC infiltration and changes in the cytokine and cellular profiles of later-stage chronic environments will be tied into their interactions with the Shh pathway. We will discuss how these changes shape tumorigenesis and tumor progression in the gastric mucosa. The current review focuses on the Shh signaling pathway and its role in the development of gastric cancer, specifically in response to Helicobacter pylori infection. We follow with an in-depth discussion of the regulation of the Hedgehog pathway during acute and chronic gastric inflammation with a focus on signaling within the MSC compartment.

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Abbreviations

Shh:

Sonic Hedgehog

Ihh:

Indian Hedgehog

Dhh:

Desert Hedgehog

Smo:

Smoothened

Ptch:

Patched

Gli1:

Glioma-associated Oncogene homolog 1

Hh:

Hedgehog

H. pylori :

Helicobacter pylori

Hp:

H. pylori

BMDC:

Bone-marrow-derived cells

MSCs:

Bone-marrow-derived mesenchymal stem cells

CDX2:

Caudal-type homeobox transcription factor 2

SDF-1:

Stromal-derived factor-1

MDSC:

Myeloid-derived suppressor cells

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Acknowledgments

We sincerely thank Glenn Doerman (Graphic Design, Illustrations, Presentations & Desktop Publishing, Departments of Cancer & Cell Biology and Molecular and Cellular Physiology, University of Cincinnati) for helping us generate Figs. 1, 2, 3, and 4. This work was supported by start-up funds (Department of Molecular and Cellular Physiology, University of Cincinnati) and from the Digestive Health Center Cincinnati Children’s Medical Health Center (DHC: Bench to Bedside Research in Pediatric Digestive Disease) Pilot and Feasibility Project Award CHTF/SUB DK078392 (Y.Z.).

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Authors and Affiliations

  1. Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert B. Sabin Way, Room 1113, MSB, Cincinnati, OH, 45267-0576, USA

    Jason Martin, Jessica M. Donnelly & Yana Zavros

  2. Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01635, USA

    JeanMarie Houghton

  3. Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01635, USA

    JeanMarie Houghton

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  1. Jason Martin
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  2. Jessica M. Donnelly
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  4. Yana Zavros
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Correspondence to Yana Zavros.

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Martin, J., Donnelly, J.M., Houghton, J. et al. The Role of Sonic Hedgehog Reemergence During Gastric Cancer. Dig Dis Sci 55, 1516–1524 (2010). https://doi.org/10.1007/s10620-010-1252-z

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