Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells.
ABSTRACT Epithelial-mesenchymal transition (EMT) refers to critical events occasionally observed during tumor progression, including invasion and metastasis, by which cancer cells acquire a fibroblast-like phenotype. Since the stromal cell-derived factor-1 (SDF-1)/CXCR4 system can facilitate lymph node metastasis in oral squamous cell carcinoma (SCC), we have explored the possibility that this system might be involved in EMT. Oral SCC cells, B88 and HNt, which have functional CXCR4 and lymph node metastatic potential, were found to lose their epithelial cell morphology due to SDF-1. In this context, the downregulation of epithelial markers, cytokeratin, E-cadherin and beta-catenin, and the upregulation of mesenchymal marker, vimentin and snail were detected. Furthermore, upregulation of vimentin by treatment with SDF-1 was impaired by phosphatidylinositol 3 kinase (PI3K) inhibitor Wortmannin, but not by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor U0126. In the type I collagen embedding culture, SDF-1-treated B88 cells formed protruding extensions, but the effect was impaired by treatment with Wortmannin. These results suggested that EMT induced by the SDF-1/CXCR4 system might be involved in the lymph node metastasis of oral SCCs via activation of PI3K-Akt/PKB pathway.
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ABSTRACT: The aim of this study is to clarify whether epithelial-mesenchymal transition (EMT) is involved in the pathogenesis and development of keratocystic odontogenic tumor (KCOT). The expression levels of EMT-related proteins and genes in normal oral mucosa (OM), radicular cyst (RC), and KCOT were determined and compared by real-time quantitative PCR and immunohistochemistry. Our data showed that the expression of epithelial markers E-cadherin and Pan-cytokeratin was significantly downregulated in KCOT with upregulation of mesenchymal markers N-cadherin compared to OM and RC. Importantly, TGF-β, a potent EMT inducer, and Slug, a master transcription factor, were also found highly expressed in KCOT. In addition, the results from Spearman rank correlation test and clustering analysis revealed the close relationship between Slug and MMP-9, which was further evidenced by double-labeling immunofluorescence that revealed a synchronous distribution for Slug with MMP-9 in KCOT samples. All the data suggested EMT might be involved in the locally aggressive behavior of KCOT.01/2015; 2015:168089. DOI:10.1155/2015/168089
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ABSTRACT: Triple negative breast cancer is known for its visceral metastasis. We have found that CXCR4 is overexpressed in triple negative breast cancer and is associated with visceral metastasis. We further investigated whether CXCR4 is a prognostic factor affecting survival following visceral metastasis in breast cancer patients. Our results indicate that increased CXCR4 expression among breast cancer patients with visceral metastasis was positively correlated with poor overall survival (P<0.001). Silencing of CXCR4 was associated with a decrease in the tumorigenic properties of MDA-MB-231 breast cancer cells, caused reversion of EMT and suppression of MMP9, increased apoptosis, and caused a reduced incidence of tumor lung metastasis in mice. These results are indicative of CXCR4 having a predictive role in patients with visceral metastasis and indicate that shRNA knock down of CXCR4 might be a novel therapeutic strategy to prevent breast cancer metastasis when CXCR4 is overexpressed.Current Molecular Medicine 11/2013; DOI:10.2174/1566524013666131121115656 · 3.61 Impact Factor
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ABSTRACT: The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer, and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared to normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and expression-cadherin expression. MiR-145 overexpression also inhibited the PI3K/Akt pathway and directly targeted AKT-3. In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate FNA samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions showed miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.Endocrine Related Cancer 04/2014; 21(4). DOI:10.1530/ERC-14-0077 · 4.91 Impact Factor