EpCAM and the biology of hepatic stem/progenitor cells.
EpCAM and the biology of hepatic stem/progenitor cells.
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DOI：
10.1152/ajpgi.00069.2014
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发表时间：
2015-02-15
期刊：
影响因子：
--
通讯作者：
van Grunsven LA
中科院分区：
文献类型：
--
作者：
Dollé L;Theise ND;Schmelzer E;Boulter L;Gires O;van Grunsven LA
上皮细胞粘附分子（EpCAM）是一种跨膜糖蛋白，其在癌、肿瘤起始细胞、选择的组织祖细胞以及胚胎和成体干细胞上频繁且高度表达。在肝脏发育过程中，EpCAM表现出动态表达，因为它可以在胎儿肝脏中检测到，包括实质细胞，而成熟肝细胞缺乏EpCAM。肝再生与导管反应内的EpCAM阳性细胞群相关，其随着成熟为肝细胞而沿着逐渐失去EpCAM的表达。EpCAM可以通过一系列策略来开启和关闭，以微调EpCAM依赖的功能和分化性状。EpCAM相关功能涉及细胞-细胞粘附、增殖、多能状态的维持、分化、迁移和侵袭的调节。这些功能可以由全长蛋白质和/或EpCAM衍生片段赋予，其在受调节的膜内蛋白水解后产生。因此，EpCAM的控制不仅取决于全长EpCAM在细胞膜上的存在，而且还取决于具有其自身调节特性的EpCAM衍生片段的形成速率的变化以及EpCAM与相互作用伴侣的缔合的变化。因此，EpCAM在未成熟肝祖细胞、转运扩增细胞和成熟肝细胞中的时空定位将决定性地影响EpCAM功能的调节，并且可能是促成干/祖细胞谱系中的适应性过程的触发因素之一。本文将总结EpCAM相关的分子事件，以及它们如何与肝胆分化和再生。
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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影响因子：
10.5
作者：
Dorrell, Craig;Erker, Laura;Grompe, Markus
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1302168110
发表时间：
2013-04-16
影响因子：
11.1
作者：
Bird, Thomas G.;Lu, Wei-Yu;Forbes, Stuart J.
通讯作者：
Forbes, Stuart J.