Slug (SNAI2) expression in oral SCC cells results in altered cell-cell adhesion and increased motility.

Oral Biology Department, College of Dentistry, The University of Nebraska Medical Center, Lincoln, NE, USA.
Cell adhesion & migration (Impact Factor: 2.34). 07/2011; 5(4):315-22.
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: According to recent studies, the function of Slug in hypoxia induced cadherin switch differs from cancer to cancer. Whether Slug is an essential mediator of the tumor hypoxia induced cadherin switch in head and neck squamous cell carcinoma (HNSCC) and the prognostic role of Slug in HNSCC patients are not elucidated. The aim of this study is to investigate the role of the Slug in cadherin switch induced by hypoxia in HNSCC. Two HNSCC cell lines and 119 HNSCC specimens were selected for the present experiments. E/N-cadherins expression and tumor cell invasion responding to hypoxia/HIF-1α overexpression and the silence of Slug/SnaI2 gene were detected in vitro. HNSCC specimens were analyzed by immunohistochemistry staining to correlate the expressions of Slug, HIF-1α and E/N-cadherins with clinical outcomes. Our research evidenced that Slug was extremely elevated in the HNSCC cells in response to hypoxia/HIF-1α overexpression. Suppressing Slug expression impaired HIF-1α induced cadherin switch and tumor invasion. In HNSCC tissues, relatively high expression of Slug was detected to be associated with endogenous HIF-1α overexpression, cadherin switch, the risk of lymph node metastasis, and a more advanced TNM stage. Additionally, aberrant Slug expression combined with HIF-1α overexpression and cadherin switch was significantly correlated with shorter HNSCC patient survival. In conclusion, Slug is necessary for hypoxia-induced cadherin switch in HNSCC and may be used as a potential risk marker in predicting HNSCC clinical outcomes.
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    ABSTRACT: Snail transcription factor has been implicated as an important regulator in epithelial-mesenchymal transition (EMT) during tumourigenesis and fibrogenesis. Our previous work showed that Snail transcription factor was activated in transforming growth factor β1 (TGF-β1) induced EMT in retinal pigment epithelial (RPE) cells and may contribute to the development of retinal fibrotic disease such as proliferative vitreoretinopathy (PVR). However, whether Snail alone has a direct role on retinal pigment epithelial-mesenchymal transition has not been investigated. Here, we analyzed the capacity of Snail to drive EMT in human RPE cells. A vector encoding Snail gene or an empty vector were transfected into human RPE cell lines ARPE-19 respectively. Snail overexpression in ARPE-19 cells resulted in EMT, which was characterized by the expected phenotypic transition from a typical epithelial morphology to mesenchymal spindle-shaped. The expression of epithelial markers E-cadherin and Zona occludin-1 (ZO-1) were down-regulated, whereas mesenchymal markers a-smooth muscle actin (a-SMA) and fibronectin were up-regulated in Snail expression vector transfected cells. In addition, ectopic expression of Snail significantly enhanced ARPE-19 cell motility and migration. The present data suggest that overexpression of Snail in ARPE-19 cells could directly trigger EMT. These results may provide novel insight into understanding the regulator role of Snail in the development of retinal pigment epithelial-mesenchymal transition.
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