2246

FGF1

Increasing evidences suggest a close association between tumor metastasis and the inflammatory factors secreted by tumor microenvironment. It has been reported that epithelial mesenchymal-transition (EMT) plays a significant role during multiple types of tumor metastasis and progression induced by inflammatory factor from tumor microenvironment. Previous researches implied that fibroblast growth factor 1 (FGF1) can promote tumor progression and cause poor prognosis in several types of malignant tumors via interacting with its receptor fibroblast growth factor receptor 1 (FGFR1). However, the effects of FGF1-FGFR1 on tongue squamous cell carcinoma (TSCC) are not yet completely understood. In the present study, we evaluated the effects and function of FGF1-FGFR1 axis on TSCC metastasis. In addition, we investigated whether the EMT pathway is involved in these effects, thus modulating the TSCC progression. The expression of FGFR1 was measured both in tongue cancer cell lines and tissues by qRT-PCR and western blot. We found that FGFR1 was up-regulated in TSCC tissues compared to non-neoplastic tongue tissues. Additionally, overexpression of FGFR1 is positively associated with poor differentiation and metastasis potential. Furthermore, the function of FGF1-FGFR1 was examined in TSCC cell line. The results implied that FGF1 can obviously promote Cal27 cells migration and invasion abilities through FGFR1, while the motile and invasive capabilities can be severely attenuated when knockdown the expression of FGFR1 by specific siRNAs. Further investigation results show that FGF1-FGFR1 axis promotes TSCC metastasis by modulating EMT pathway. However, this effect can be inhibited by blocking the FGF1-FGFR1 axis using FGFR1 specific siRNAs. In conclusion, our findings of the present study provide the evidences that FGF1-FGFR1 axis promotes the TSCC metastasis through the EMT pathway.CI - Copyright (c) 2015 Elsevier Inc. All rights reserved.

During epithelial-mesenchymal transition (EMT), epithelial cells are converted into isolated motile and invasive mesenchymal cells. In model systems, EMT is induced most often by the activation of tyrosine kinase receptors through signaling pathways involving translational and post-translational regulation. In this study, we have used the NBT-II bladder carcinoma cell system to investigate in vitro Fibroblast Growth Factor-1 (FGF-1)-induced EMT. Transcriptome analyses were performed on NBT-II cells stimulated for 2, 6, 24, and 48 h with FGF-1. As some phenotypic changes occurred around 6 h post-stimulation, a supervised analysis was designed to identify transcript variations across defined time-periods. Our results clearly indicate that immediately after FGF-1 stimulation a set of genes assigned to transcriptional regulation (e.g., jun-B and v-ets) and to EMT induction (e.g., Notch 1) is transiently up-regulated. A set of genes involved in proteolytic systems (e.g., MMP-13 and uPAR) is immediately up-regulated but subsequently maintained throughout FGF-1 stimulation. Then follows a second wave of gene expression that includes a strong but transient up-regulation of ephrin B1 and arginase I. Finally, a third group of genes is stably modulated over 48 h which consists primarily of down-regulated genes specifically associated with the EMT-based loss of the epithelial phenotype and maintenance of the mesenchymal and invasive phenotype of carcinoma cells. Using genome-wide oligoarray technology, we have identified novel expressions of immediate, immediate-early and later EMT biomarkers that are specifically activated downstream of the FGF/FGFR pathway and which might be significant prognostic factors for tumor progression of carcinoma.