title: EpCAM and the biology of hepatic stem/progenitor cells.
abstract: Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein, which is frequently and highly expressed on carcinomas, tumor-initiating cells, selected tissue progenitors, and embryonic and adult stem cells. During liver development, EpCAM demonstrates a dynamic expression, since it can be detected in fetal liver, including cells of the parenchyma, whereas mature hepatocytes are devoid of EpCAM. Liver regeneration is associated with a population of EpCAM-positive cells within ductular reactions, which gradually lose the expression of EpCAM along with maturation into hepatocytes. EpCAM can be switched on and off through a wide panel of strategies to fine-tune EpCAM-dependent functional and differentiative traits. EpCAM-associated functions relate to cell-cell adhesion, proliferation, maintenance of a pluripotent state, regulation of differentiation, migration, and invasion. These functions can be conferred by the full-length protein and/or EpCAM-derived fragments, which are generated upon regulated intramembrane proteolysis. Control by EpCAM therefore not only depends on the presence of full-length EpCAM at cellular membranes but also on varying rates of the formation of EpCAM-derived fragments that have their own regulatory properties and on changes in the association of EpCAM with interaction partners. Thus spatiotemporal localization of EpCAM in immature liver progenitors, transit-amplifying cells, and mature liver cells will decisively impact the regulation of EpCAM functions and might be one of the triggers that contributes to the adaptive processes in stem/progenitor cell lineages. This review will summarize EpCAM-related molecular events and how they relate to hepatobiliary differentiation and regeneration.
authors.affiliation: Department of Biomedical Sciences, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels, Belgium; ldolle@vub.ac.be.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dollé
authors.affiliation: Departments of Pathology and Medicine, Beth Israel Medical Center of Albert Einstein College of Medicine, New York, New York;
authors.forename: Neil D
authors.initials: ND
authors.lastname: Theise
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Eva
authors.initials: E
authors.lastname: Schmelzer
authors.affiliation: Medical Research Council Human Genetics Unit, Institute for Genetics and Molecular Medicine, Edinburgh, Scotland; and.
authors.forename: Luke
authors.initials: L
authors.lastname: Boulter
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gires
authors.affiliation: Department of Biomedical Sciences, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels, Belgium;
authors.forename: Leo A
authors.initials: LA
authors.lastname: van Grunsven
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D000071858:Epithelial Cell Adhesion Molecule; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008115:Liver Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule
keywords: EpCAM; hepatic stem/progenitor cell; liver differentiation; liver regeneration; signaling