Oral Biology Department, College of Dentistry, The University of Nebraska Medical Center, Lincoln, NE, USA.
Cell Adh Migr. 2011 Jul-Aug;5(4):315-22. doi: 10.4161/cam.5.4.17040. Epub 2011 Jul 1.
The Snail family of zinc finger transcription factors plays an important role in epithelial to mesenchymal transition (EMT) in a variety of tissues and systems. Slug (SNAI2) expression has been shown to directly contribute to a subset of events required for EMT in events such as re-epithelialization during wound healing and neural crest cell migration. In addition, slug expression was shown to correlate with disease recurrence in head and neck squamous cell carcinoma (HNSCC) patients. Based on this association we chose to specifically examine the effects of exogenous slug expression in HNSCC cells and specifically assess adhesive junction assembly and the motility characteristics in these cells. Slug expression led to changes in adherens junction and desmosome assembly characterized by a classical cadherin switch and loss of desmosome assembly. Additionally, we performed gene expression profiling to identify novel slug dependent gene expression changes in a HNSCC cell line. In addition to genes known to be altered during EMT, we identified a novel set of Slug responsive genes that will provide a better understanding of slug overexpression during EMT and HNSCC progression.
蜗牛家族的锌指转录因子在多种组织和系统中的上皮间质转化(EMT)中发挥重要作用。Slug(SNAI2)的表达已被证明直接促成 EMT 所必需的事件中的一部分,例如在伤口愈合和神经嵴细胞迁移过程中的再上皮化。此外,Slug 的表达与头颈部鳞状细胞癌(HNSCC)患者的疾病复发相关。基于这种关联,我们选择专门研究外源性 Slug 在 HNSCC 细胞中的表达对这些细胞的粘着连接组装和运动特性的影响。Slug 的表达导致粘着连接和桥粒连接组装的变化,其特征是经典的钙粘蛋白转换和桥粒连接组装的丧失。此外,我们进行了基因表达谱分析,以鉴定 HNSCC 细胞系中与 Slug 相关的新的基因表达变化。除了已知在 EMT 期间发生改变的基因外,我们还鉴定了一组新的 Slug 反应基因,这将更好地理解 EMT 和 HNSCC 进展过程中 Slug 的过表达。