Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins.
Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins.
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DOI：
10.1083/jcb.139.5.1337
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发表时间：
1997-12-01
期刊：
影响因子：
--
通讯作者：
Warnaar SO
中科院分区：
文献类型：
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作者：
Litvinov SV;Balzar M;Winter MJ;Bakker HA;Briaire-de Bruijn IH;Prins F;Fleuren GJ;Warnaar SO
非钙粘蛋白型，钙离子非依赖性细胞间粘附分子的上皮组织的组织的贡献是，到目前为止，还不清楚。一种嗜同性的上皮钙非依赖性粘附分子（Ep-CAM）在大多数上皮细胞、良性或恶性增生性病变或胚胎发育过程中表达。在这里，我们表明，异位Ep-CAM，当在经典的钙粘蛋白（E-或N-钙粘蛋白）相互连接的细胞中表达时，诱导分离的转染子从亲本细胞类型的共聚集测定和培养的混合聚集体，分别。在后一种测定中，与亲本细胞相比，Ep-CAM阳性转染子表现得像具有降低的细胞-细胞粘附强度的细胞。使用可诱导的Ep-CAM-cDNA构建体的转染子，我们证明了在钙粘蛋白阳性细胞中Ep-CAM表达的增加导致粘附连接的逐渐废除。Ep-CAM的过表达对细胞钙粘蛋白的总量没有影响，但影响钙粘蛋白与细胞骨架的相互作用，因为观察到钙粘蛋白分子的洗涤剂不溶性部分大幅减少。同样，α-和β-连环蛋白的洗涤剂不溶性部分在过表达Ep-CAM的细胞中减少。虽然总β-连环蛋白含量保持不变，但随着Ep-CAM表达增加，观察到总细胞α-连环蛋白减少。随着钙粘蛋白介导的细胞间粘附减少，Ep-CAM介导的细胞间连接成为主导。缺乏胞质结构域的Ep-CAM的粘附缺陷突变体对钙粘蛋白介导的细胞-细胞粘附没有影响。Ep-CAM调节钙粘蛋白介导的细胞-细胞相互作用的能力，如本研究所示，表明该分子在上皮细胞的增殖和可能的恶性表型的发展中的作用，因为在体内观察到Ep-CAM表达的增加与上皮细胞的增生和恶性增殖相关。
The contribution of noncadherin-type, Ca2+-independent cell–cell adhesion molecules to the organization of epithelial tissues is, as yet, unclear. A homophilic, epithelial Ca2+-independent adhesion molecule (Ep-CAM) is expressed in most epithelia, benign or malignant proliferative lesions, or during embryogenesis. Here we demonstrate that ectopic Ep-CAM, when expressed in cells interconnected by classic cadherins (E- or N-cadherin), induces segregation of the transfectants from the parental cell type in coaggregation assays and in cultured mixed aggregates, respectively. In the latter assay, Ep-CAM–positive transfectants behave like cells with a decreased strength of cell–cell adhesion as compared to the parental cells. Using transfectants with an inducible Ep-CAM–cDNA construct, we demonstrate that increasing expression of Ep-CAM in cadherin-positive cells leads to the gradual abrogation of adherens junctions. Overexpression of Ep-CAM has no influence on the total amount of cellular cadherin, but affects the interaction of cadherins with the cytoskeleton since a substantial decrease in the detergent-insoluble fraction of cadherin molecules was observed. Similarly, the detergent-insoluble fractions of α- and β-catenins decreased in cells overexpressing Ep-CAM. While the total β-catenin content remains unchanged, a reduction in total cellular α-catenin is observed as Ep-CAM expression increases. As the cadherin-mediated cell–cell adhesions diminish, Ep-CAM–mediated intercellular connections become predominant. An adhesion-defective mutant of Ep-CAM lacking the cytoplasmic domain has no effect on the cadherin-mediated cell–cell adhesions. The ability of Ep-CAM to modulate the cadherin-mediated cell–cell interactions, as demonstrated in the present study, suggests a role for this molecule in development of the proliferative, and probably malignant, phenotype of epithelial cells, since an increase of Ep-CAM expression was observed in vivo in association with hyperplastic and malignant proliferation of epithelial cells.