EMT allows a polarized epithelium to lose epithelial integrity and acquire mesenchymal characteristics. Previously, we found that overexpression of the intracellular domain of Notch3 (N3ICD) can inhibit EMT in breast cancer cells. In this study, we aimed to elucidate the influence of N3ICD or N3ICD combined with the transmembrane domain (TD+N3ICD) on the expression and distribution of TJs/AJs and polar molecules. We found that although N3ICD can upregulate the expression levels of the above-mentioned molecules, TD+N3ICD can inhibit EMT more effectively than N3ICD alone. TD+N3ICD overexpression upregulated the expression of endogenous full-length Notch3 and contributed to correcting the position of TJs/AJs molecules and better acinar structures formation. Co-immunoprecipitation results showed that the upregulated endogenous full-length Notch3 could physically interact with E-ca in MDA-MB-231/pCMV-(TD+N3ICD) cells. Collectively, our data indicate that overexpression of TD+N3ICD can effectively inhibit EMT, resulting in better positioning of TJs/AJs molecules and cell-cell adhesion in breast cancer cells. Abbreviations: EMT: Epithelial-mesenchymal transition; TJs: Tight junctions; AJs: Adherens junctions; aPKC: Atypical protein kinase C; Crb: Crumbs; Lgl: Lethal (2) giant larvae; LLGL2: lethal giant larvae homolog 2; PAR: Partitioning defective; PATJ: Pals1-associated TJ protein.

中文翻译：

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具有跨膜结构域的N3ICD可通过纠正紧密/粘附连接的位置来有效抑制EMT。

EMT使极化的上皮失去上皮的完整性并获得间充质特征。以前，我们发现Notch3（N3ICD）的胞内域的过度表达可以抑制乳腺癌细胞中的EMT。在这项研究中，我们旨在阐明N3ICD或N3ICD结合跨膜结构域（TD + N3ICD）对TJ / AJ和极性分子的表达和分布的影响。我们发现，尽管N3ICD可以上调上述分子的表达水平，但TD + N3ICD可以比单独使用N3ICD更有效地抑制EMT。TD + N3ICD的过表达上调了内源性全长Notch3的表达，并有助于纠正TJs / AJs分子的位置和更好的腺泡结构形成。免疫共沉淀结果表明，MDA-MB-231 / pCMV-（TD + N3ICD）细胞中上调的内源性全长Notch3可以与E-ca发生物理相互作用。总体而言，我们的数据表明TD + N3ICD的过表达可以有效抑制EMT，从而导致TJ / AJs分子的定位更好，并使乳腺癌细胞中的细胞粘附。缩写：EMT：上皮-间质转化；TJ：紧密连接；AJs：Adherens交界处；aPKC：非典型蛋白激酶C；Crb：碎屑；Lgl：致命的（2）巨型幼虫；LLGL2：致死的巨型幼虫同源物2；PAR：分区有缺陷；PATJ：与Pals1相关的TJ蛋白。导致TJ / AJs分子在乳腺癌细胞中的更好定位以及细胞与细胞的粘附。缩写：EMT：上皮-间质转化；TJ：紧密连接；AJs：Adherens交界处；aPKC：非典型蛋白激酶C；Crb：碎屑；Lgl：致命的（2）巨型幼虫；LLGL2：致死的巨型幼虫同源物2；PAR：分区有缺陷；PATJ：与Pals1相关的TJ蛋白。导致TJ / AJs分子在乳腺癌细胞中的更好定位以及细胞与细胞的粘附。缩写：EMT：上皮-间质转化；TJ：紧密连接；AJs：Adherens交界处；aPKC：非典型蛋白激酶C；Crb：碎屑；Lgl：致命的（2）巨型幼虫；LLGL2：致死的巨型幼虫同源物2；PAR：分区有缺陷；PATJ：与Pals1相关的TJ蛋白。