相互作用组分析揭示了上皮细胞黏附分子（EpCAM）在胚胎干细胞和癌细胞分化过程中的内吞作用和膜循环。
Interactome analysis reveals endocytosis and membrane recycling of EpCAM during differentiation of embryonic stem cells and carcinoma cells.
作者信息
Pan Min, Kohlbauer Vera, Blancke Soares Alexandra, Schinke Henrik, Huang Yuanchi, Kranz Gisela, Quadt Tanja, Hachmeister Matthias, Gires Olivier
机构信息
Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China.
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, LMU Munich, Munich, Germany.
出版信息
iScience. 2021 Sep 27;24(10):103179. doi: 10.1016/j.isci.2021.103179. eCollection 2021 Oct 22.
Transmembrane epithelial cell adhesion molecule (EpCAM) is expressed in epithelia, carcinoma, teratoma, and embryonic stem cells (ESCs). EpCAM displays spatiotemporal patterning during embryogenesis, tissue morphogenesis, cell differentiation, and epithelial-to-mesenchymal transition (EMT) in carcinomas. Potential interactors of EpCAM were identified in murine F9 teratoma cells using a stable isotope labeling with amino acids in cell culture-based proteomic approach (n = 77, enrichment factor >3, p value ≤ 0.05). Kyoto Encyclopedia of Genes and Genomes and gene ontology terms revealed interactions with regulators of endosomal trafficking and membrane recycling, which were further validated for Rab5, Rab7, and Rab11. Endocytosis and membrane recycling of EpCAM were confirmed in mF9 cells, E14TG2α ESC, and Kyse30 carcinoma cells. Reduction of EpCAM during mesodermal differentiation and TGFβ-induced EMT correlated with enhanced endocytosis and block or reduction of recycling in ESCs and esophageal carcinoma cells. Hence, endocytosis and membrane recycling are means of regulation of EpCAM protein levels during differentiation of ESC and EMT induction in carcinoma cells.
跨膜上皮细胞粘附分子（EpCAM）在上皮细胞、癌组织、畸胎瘤和胚胎干细胞（ESC）中表达。在胚胎发生、组织形态发生、细胞分化以及癌组织中的上皮-间质转化（EMT）过程中，EpCAM呈现出时空模式。使用基于细胞培养的蛋白质组学方法中的氨基酸稳定同位素标记技术，在小鼠F9畸胎瘤细胞中鉴定出EpCAM的潜在相互作用分子（n = 77，富集因子>3，p值≤0.05）。京都基因与基因组百科全书（KEGG）和基因本体论（GO）术语显示，其与内体运输和膜回收的调节因子存在相互作用，这在Rab5、Rab7和Rab11中得到了进一步验证。在mF9细胞、E14TG2α ESC和Kyse30癌细胞中证实了EpCAM的内吞作用和膜回收。在中胚层分化和TGFβ诱导的EMT过程中，EpCAM的减少与ESC和食管癌细胞内吞作用增强以及回收受阻或减少相关。因此，内吞作用和膜回收是ESC分化和癌细胞EMT诱导过程中调节EpCAM蛋白水平的方式。
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