Astrocyte Elevated Gene-1 Promotes Progression of Cervical Squamous Cell Carcinoma by Inducing Epithelial-Mesenchymal Transition via Wnt Signaling

Abstract

ObjectiveThe 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.MethodsThe 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.ResultsAEG-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.ConclusionsAEG-1 was associated with the progression of CSCC by promoting epithelial-mesenchymal transition via Wnt signaling pathway.

MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by targeting AEG-1 in cervical cancer

“…AEG-1 promoted cell proliferation through the FOXO1/PI3K/AKT signaling pathway in breast cancer (29). AEG-1 induced epithelial-mesenchymal transition through the activation of Wnt/β-catenin signaling in lung cancer and cervical squamous cell carcinoma (30,31). In CC, AEG-1 knockdown decreased its invasiveness, EMT and chemoresistance (32).…”

Association of MTDH immunohistochemical expression with metastasis and prognosis in female reproduction malignancies: a systematic review and meta-analysis

“…Another 50 studies were excluded for lacking survival data or using cell lines to explore the impact of MTDH on biological characteristics, mechanisms and pathways of reproduction malignancies. Finally, a total of 19 studies (17 English articles and 2 Chinese articles)5678141516171819202122232425262728 published from 2008 to 2016 were included in our meta-analysis (Fig. 1).…”

“…Among them 8 studies were about breast cancer514151621232528, while 7 were about ovarian cancer6171820222627, 3 about cervical cancer71924 and 1 about endometrial cancer8.…”

“…As for inclusion criteria, all the samples of included studies were tissues and their MTDH expression was examined by immunohistochemical (IHC). Eleven studies5681516171821232526 defined staining index (SI) ≥ 4 as cut-off value of positive expression while the other 8 studies714192022242728 did not. The follow-up time ranged from 36 to 180 months.…”

“…For survival analysis, 14 studies567814161718202324252627 examined the association of MTDH expression with mortality and 8 studies68162024252728 were available for disease-free survival (DFS). The concomitant variables of multivariate analysis were list in Table 2.…”