Tanaka Shoko, Kobayashi Wakako, Haraguchi Misako, Ishihata Kiyohide, Nakamura Norifumi, Ozawa Masayuki
Department of Biochemistry and Molecular Biology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Biochem Biophys Rep. 2016 Aug 20;8:120-126. doi: 10.1016/j.bbrep.2016.08.017. eCollection 2016 Dec.
The epithelial-mesenchymal transition (EMT) is a fundamental characteristic of carcinoma cells. EMT is generally associated with a change in cellular morphology from cobblestone to spindle shape, reduced expression of epithelial markers such as E-cadherin, and enhanced expression of mesenchymal markers such as N-cadherin. This EMT-associated reciprocal expression of E-cadherin and N-cadherin has been called the "cadherin switch". Downregulation of E-cadherin enables cells to dissociate from colonies while upregulation of N-cadherin is associated with increased invasiveness. The transcription factor Snail1 induces these changes in various epithelial cell lines, including canine MDCK cells and human A431 cells. In the present study, we introduced a Snail1 expression vector into human DLD-1 cells and isolated stable transfectants. These cells showed changes in morphology, reduced expression of epithelial marker E-cadherin and occludin, and elevated invasion and migration. However, neither expression of N-cadherin protein nor its corresponding mRNA was detected. Therefore, elevated N-cadherin expression is not required for invasiveness of the cells.
上皮-间质转化(EMT)是癌细胞的一个基本特征。EMT通常与细胞形态从鹅卵石样变为纺锤形、上皮标志物(如E-钙黏蛋白)表达降低以及间质标志物(如N-钙黏蛋白)表达增强有关。这种与EMT相关的E-钙黏蛋白和N-钙黏蛋白的相互表达被称为“钙黏蛋白转换”。E-钙黏蛋白的下调使细胞能够从集落中解离,而N-钙黏蛋白的上调与侵袭性增加有关。转录因子Snail1在包括犬MDCK细胞和人A431细胞在内的各种上皮细胞系中诱导这些变化。在本研究中,我们将Snail1表达载体导入人DLD-1细胞并分离出稳定转染子。这些细胞表现出形态变化、上皮标志物E-钙黏蛋白和闭合蛋白表达降低以及侵袭和迁移增加。然而,未检测到N-钙黏蛋白蛋白及其相应mRNA的表达。因此,细胞的侵袭性并不需要N-钙黏蛋白表达升高。