title: Hedgehog signalling in cancer.
abstract: Hedgehog signalling is a key regulator of embryonic development controlling proliferation and/or cell fate determination. With identification of the Hedgehog receptor PTCH1 as a tumour suppressor gene that underlies the human nevoid basal cell carcinoma syndrome (NBCCS), the Hedgehog signalling pathway was firmly linked to cancer. It now appears that constitutive activation of Hedgehog signalling, by inactivating mutations in PTCH1 or activating mutations in the coreceptor SMOH, is required and possibly sufficient for basal cell carcinoma development and also contributes to the formation of a variety of other tumour types, including medulloblastoma and rhabdomyosarcoma. Several lines of evidence, including transgenic mice experiments, suggest that the critical cellular effect is stimulation of proliferation mediated by the transcriptional effector GLI1. Additional components of the signal transduction machinery as well as essential target genes remain to be identified, and involvement of the Hedgehog signalling pathway in other tumour types and/or hereditary cancer predisposition syndromes is to be expected.
authors.affiliation: Karolinska Institutet, Department of Biosciences and Center for Nutrition and Toxicology, Huddinge, Sweden. rune.toftgard@cnt.ki.se
authors.forename: R
authors.initials: R
authors.lastname: Toftgård
mesh_terms: D000818:Animals; D002280:Basal Cell Carcinoma / Q000209:etiology / Q000235:genetics; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D006801:Humans; D019476:Insect Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D015513:Oncogene Proteins / Q000502:physiology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics; D000072086:Smoothened Receptor; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology; D000071676:Zinc Finger Protein GLI1
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D015513:Oncogene Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C100664:smo protein, Drosophila; C077245:hh protein, Drosophila