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EpCAM and the biology of hepatic stem/progenitor cells

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  • Laurent Dollé
  • Neil D Theise
  • Eva Schmelzer
  • Luke Boulter
  • Olivier Gires
  • Leo A van Grunsven

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    Rights statement: Copyright © 2015 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0: © the American Physiological Society.

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http://ajpgi.physiology.org/content/308/4/G233
Original languageEnglish
Pages (from-to)G233-G250
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume308
Issue number4
DOIs
Publication statusPublished - 15 Feb 2015

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.

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