title: Langerhans' cell histiocytosis is caused by dysregulation of the E-cadherin-beta-catenin cascade: a hypothesis.
abstract: Langerhans' cell histiocytosis (LCH) is a proliferative disease of cells of the dendritic cell lineage, closely resembling activated Langerhans' cells. The clinical picture of LCH is greatly variable, suggesting a scale of aberrancies at the cellular level. Despite progress in clinical treatment, the aetiology and pathogenesis of this disease remain unknown. In the present paper, we present the hypothesis that dysregulation of the E-cadherin-beta-catenin-Wnt cascade, which has both adhesive and transcriptional functions, may be fundamental to the development of LCH. This hypothesis is founded upon two notions: (i) careful regulation of this cascade is essential in normal Langerhans cell activation; and (ii) abnormalities in the E-cadherin-beta-catenin cascade are a major cause of epithelial neoplastic proliferation. On the basis of this hypothesis, we present three alternative scenarios that may describe the initial steps in the pathogenesis of LCH.
authors.affiliation: Department of Immunology, Erasmus University, Rotterdam, The Netherlands. leenen@immu.fgg.eur.nl
authors.forename: P J
authors.initials: PJ
authors.lastname: Leenen
authors.forename: R M
authors.initials: RM
authors.lastname: Egeler
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D006646:Histiocytosis, Langerhans-Cell / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000502:physiology*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015534:Trans-Activators; D051154:Wnt2 Protein; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051154:Wnt2 Protein; D051176:beta Catenin