Objective: The aim of this study was to investigate the association of astrocyte elevated gene-1 (AEG-1) with epithelial-mesenchymal transition of cervical squamous cell carcinoma (CSCC) and the underlying mechanisms.
Methods: The expression of proteins was determined by immunohistochemistry in tissues. Overexpression and knockdown of AEG-1 in SiHa cells were achieved by stable AEG-1 gene transfection (SiHa-AEG-1+) and AEG-1-siRNA (SiHa-AEG-1-), respectively. The cellular levels of messenger RNA and proteins were assessed with reverse transcription polymerase chain reaction and Western blotting, respectively. The cell invasion capacity was assessed by the chamber invasion assay.
Results: AEG-1 was overexpressed in clinical CSCC and associated with lymph node metastasis, parametrial involvement, stromal invasion, and vascular invasion. A high level of vimentin and a low level of E-cadherin were also detected in the cancer tissues. AEG-1 expression was positively correlated with vimentin expression and negatively with E-cadherin expression in CSCC tissues. In addition, high level of AEG-1 was related to unfavorable prognosis of CSCC. On a cellular level, overexpression of AEG-1 was found to lead to an up-regulation of vimentin and a down-regulation of E-cadherin on messenger RNA and protein level in SiHa cells, whereas AEG-1 knockdown led to a contrary result. Meanwhile, the nuclear levels of NF-κB p65 and β-catenin were also increased in SiHa-AEG-1+, whereas their nuclear levels were decreased in SiHa-AEG-1-. Inhibition of Wnt signaling significantly reduced vimentin level and enhanced E-cadherin level in SiHa-AEG+, but inhibition of NF-κB signaling did not. SiHa-AEG-1+ and SiHa-AEG- showed an enhanced and a decreased invasive capacity, respectively. The enhanced invasiveness of SiHa-AEG-1+ was weakened by inhibition of Wnt signaling.
Conclusions: AEG-1 was associated with the progression of CSCC by promoting epithelial-mesenchymal transition via Wnt signaling pathway.