EpCAM and the biology of hepatic stem/progenitor cells

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 308; no. 4; pp. G233 - G250
• Main Authors: Dollé, Laurent, Theise, Neil D., Schmelzer, Eva, Boulter, Luke, Gires, Olivier, van Grunsven, Leo A.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 15.02.2015
• Series: Intestinal Stem Cells in GI Physiology and Disease
• Subjects: Animals; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Call for Papers; Cell adhesion & migration; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Differentiation; Cell Lineage; Cell Proliferation; Cellular biology; Epithelial Cell Adhesion Molecule; Gene Expression Regulation, Developmental; Glycoproteins; Hepatocytes - metabolism; Hepatocytes - pathology; Humans; Liver - metabolism; Liver - pathology; Liver - physiopathology; Liver Diseases - metabolism; Liver Diseases - pathology; Liver Diseases - physiopathology; Liver Regeneration; Membranes; Physiology; Protein expression; Signal Transduction; Stem cells; Stem Cells - metabolism; Stem Cells - pathology; signaling; EpCAM; hepatic stem/progenitor cell; liver differentiation; liver regeneration
• ISSN: 0193-1857; 1522-1547; 1522-1547
• DOI: 10.1152/ajpgi.00069.2014

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.