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首页> 外文期刊>Journal of Cellular Physiology >Identification of a Novel Human E-Cadherin Splice Variant and Assessment of Its Effects Upon EMT-Related Events
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Identification of a Novel Human E-Cadherin Splice Variant and Assessment of Its Effects Upon EMT-Related Events

机译：识别人类上皮型接头的小说变体和评估其影响EMT-Related事件

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Epithelial Cadherin (E-cadherin) is involved in calcium-dependent cell-cell adhesion and signal transduction. The E-cadherin decrease/loss is a hallmark of Epithelial to Mesenchymal Transition (EMT), a key event in tumor progression. The underlying molecular mechanisms that trigger E-cadherin loss and consequent EMT have not been completely elucidated. This study reports the identification of a novel human E-cadherin variant mRNA produced by alternative splicing. A bioinformatics evaluation of the novel mRNA sequence and biochemical verifications suggest its regulation by Nonsense-Mediated mRNA Decay (NMD). The novel E-cadherin variant was detected in 29/42 (69%) human tumor cell lines, expressed at variable levels (E-cadherin variant expression relative to the wild type mRNA = 0.05-11.6%). Stable transfection of the novel E-cadherin variant in MCF-7 cells (MCF7Ecadvar) resulted in downregulation of wild type E-cadherin expression (transcript/protein) and EMT-related changes, among them acquisition of a fibroblastic-like cell phenotype, increased expression of Twist, Snail, Zeb1, and Slug transcriptional repressors and decreased expression of ESRP1 and ESRP2 RNA binding proteins. Moreover, loss of cytokeratins and gain of vimentin, N-cadherin and Dysadherin/FXYD5 proteins was observed. Dramatic changes in cell behavior were found in MCF7Ecadvar, as judged by the decreased cell-cell adhesion (Hanging-drop assay), increased cell motility (Wound Healing) and increased cell migration (Transwell) and invasion (Transwell w/Matrigel). Some changes were found in MCF-7 cells incubated with culture medium supplemented with conditioned medium from HEK-293 cells transfected with the E-cadherin variant mRNA. Further characterization of the novel E-cadherin variant will help understanding the molecular basis of tumor progression and improve cancer diagnosis.(C) 2016 Wiley Periodicals, Inc.
机译：上皮钙粘蛋白(钙)参与calcium-dependent信息粘附和信号转导。上皮间充质转变的标志(EMT)肿瘤恶化的关键事件。内在的分子机制触发钙粘蛋白和顺向EMT没有损失完全阐明。识别人类上皮型小说可变剪接产生的变体mRNA。生物信息学评价小说的信使rna序列和生化验证建议其监管Nonsense-Mediated mRNA衰变(NMD)。在人类肿瘤细胞系,29/42(69%)的表达在变量的水平(钙粘蛋白变体表达式相对于野生型mRNA = 0.05 -11.6%)。钙粘蛋白稳定转染的小说变体MCF-7细胞(MCF7Ecadvar)导致downregulation野生型的钙粘蛋白的表达(成绩单/蛋白质)和EMT-related变化,其中fibroblastic-like的收购细胞表型,增加扭曲的表情,蜗牛、Zeb1和蛞蝓转录阻遏物和减少ESRP1 ESRP2 RNA的表达结合蛋白。波形蛋白的获得,N-cadherin和Dysadherin / FXYD5蛋白质被观察到。细胞行为的变化被发现MCF7Ecadvar,根据信息的减少粘连(悬滴试验),增加细胞运动性(伤口愈合)和增加细胞迁移(Transwell)和入侵(Transwellw /人工基底膜)。细胞培养基补充孵化从hek - 293细胞条件培养基转染的mRNA钙粘蛋白变体。小说钙粘蛋白的进一步描述变体将有助于理解分子癌症肿瘤恶化和改善的基础诊断。(C) 2016年威利期刊、公司。

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