期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 308, 期 4, 页码 G233-G250出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00069.2014
关键词
EpCAM; liver differentiation; liver regeneration; hepatic stem/progenitor cell; signaling
资金
- Interuniversity Attraction Poles (IAP), Phase VII (Federal Science Policy, BELSPO) [P7/47]
- Hepstem: IWT-SBO (Flemish Government) [090066]
- Brustem: Impulse Program, Brustem (Brussels government) [2011-IP-LS-104]
- Deutsche Forschungsgemeinschaft [GI 540-3/1]
- Forderung von Forschung und Lehre (Ludwig-Maximilians-University Munich)
- Wilhelm-Sander-Stiftung [2009.083.1, 2012.051.1]
- National Heart, Lung, and Blood Institute [R01HL108631]
- University of Pittsburgh Medical Center
- Leverhulme Trust
- Medical Research Council
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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