title: Inhibition of Hedgehog signaling in the gastrointestinal tract: targeting the cancer microenvironment.
abstract: This review summarizes emerging information regarding the Hedgehog (Hh) signaling pathway during neoplastic transformation in the gastrointestinal tract. Although there is a role for the well-established canonical pathway in which Hedgehog ligands interact with their receptor Patched, there is sufficient evidence that downstream components of the Hh pathway, e.g., Gli1, are hijacked by non-Hh signaling pathways to promote the conversion of the epithelium to dysplasia and carcinoma. We review the canonical pathway and involvement of primary cilia, and then focus on current evidence for Hh signaling in luminal bowel cancers as well as accessory organs, i.e., liver, pancreas and biliary ducts. We conclude that targeting the Hh pathway with small molecules, nutriceuticals and other mechanisms will likely require a combination of inhibitors that target Gli transcription factors in addition to canonical modulators such as Smoothened.
authors.affiliation: Departments of Internal Medicine and Molecular and Integrative Physiology, Division of Gastroenterology, University of Michigan, United States. Electronic address: merchanj@umich.edu.
authors.forename: Juanita L
authors.initials: JL
authors.lastname: Merchant
authors.forename: Milena
authors.initials: M
authors.lastname: Saqui-Salces
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D004067:Digestive System Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D053823:Hedgehog Proteins
keywords: Gli1; MDSCs; Primary cilia; Stomach; Stroma