Astrocyte elevated gene-1 promotes the proliferation and invasion of breast cancer cells by activating the Wnt/β-catenin signaling pathway

Abstract

Abstract. Astrocyte elevated gene-1 (AEG1) was identified to be overexpressed in breast cancer, and to be associated with the development of breast cancer. In the present study, AEG1 was identified as highly expressed in the MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines and was detected in the MCF-10A normal breast epithelial cell line. The present study established an AEG1-knockdown MCF-7 cell line to investigate the expression status of certain cancer-associated proteins. Western blotting demonstrated that AEG1 may affect cancer cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway, a hypothesis that has been supported by cell function tests. The results of the present study demonstrated that when AEG1 was significantly overexpressed in breast cancer cells it promoted cell proliferation and invasion via activating the Wnt/β-catenin signaling pathway. Therefore, AEG1 may serve as a novel therapeutic target in breast cancer. IntroductionBreast cancer is a common type of malignancy; the incidence of the disease has increased in recent years worldwide, currently ranking first with respect to cancer-associated morbidity in women (1-3). The traditional methods of treatment include surgery, radiotherapy and chemotherapy for patients with advanced breast cancer exhibit poor efficacy (4). Therefore, the development of gene-targeted therapy for breast cancer requires further attention. Previous studies have revealed that numerous genes are involved in the occurrence and development of breast cancer, including cyclin D1, matrix metalloproteinases (MMPs) and E-cadherin (5-8). Astrocyte elevated gene-1 (AEG1) has also been investigated with respect to poor prognosis in breast cancer (9). AEG1 is a potentially crucial mediator of tumor malignancy and a key converging point of a complex network of oncogenic signaling pathways (10-12). Previous studies revealed that the AEG1 gene was significantly overexpressed in a number of types of malignant cells, and is associated with tumorigenesis, proliferation, invasion and metastasis (13,14). Statistics also demonstrated that AEG1 was upregulated in breast cancer tissue and positively correlated with clinical stage and lymph node metastasis (15).The Wnt signaling pathway is one of the most important intracellular signal transduction pathways, and it affects the activated state of multiple effector molecules downstream (16)(17)(18)(19). It is closely associated with a variety of human tumor developments, and serves an important role in breast cancer cell proliferation and invasion (20,21). However, the mechanisms that underlie the activation of the Wnt signaling pathway in various types of breast cancer have yet to be identified. β-catenin has been revealed as a central regulator in the Wnt signaling pathway, and is associated with disease progression and poor prognosis in breast cancer (22). Typically, during activation of the Wnt signaling pathway, β-catenin accumulates in the cytosol at high levels, binds to T-cell factor/lymphoid enhancer fac...

<p>MicroRNA 885-5p Inhibits Hepatocellular Carcinoma Metastasis by Repressing AEG1</p>

“…Overexpression of AEG1 has been documented to be involved in many tumors' biological processes, including tumor proliferation, metastasis, EMT. [12][13][14][15] To evaluate the possibility that AEG1 is important for HCC, we examined AEG1 expression in corresponding noncancerous tissues and HCC using Gene Expression Profiling Interactive Analysis (GEPIA) website based on TCGA database. 16 Notably, AEG1 expression in HCC samples was significantly higher compared to normal samples ( Figure 3A).…”

Clinical Significance and Prognosis Value of Wnt Signaling Pathway in Cervical Cancer

“…In another study, using TOP‐Flash reporter assay and Western blot was indicated that SOX14 remarkable activated Wnt/β‐catenin signaling. The authors demonstrated that SOX14 can promote proliferation and invasion capacity of CC cell lines (HT‐3, Caski, HeLa, and SiHa) by activating the Wnt/β‐catenin cascade [Li et al, ]. In one study which seeks novel approach for modulating cisplatin sensitivity in CC achieved interesting results.…”

Long Noncoding RNA Taurine-Upregulated Gene1 (TUG1) Promotes Tumor Growth and Metastasis Through TUG1/Mir-129-5p/Astrocyte-Elevated Gene-1 (AEG-1) Axis in Malignant Melanoma

“…Astrocyte-elevated gene-1 (AEG-1) is encoded on chromosome 8q22 [ 14 ], and upregulation of AEG1 was confirmed in various malignant tumors [ 15 , 16 ]. In addition, aberrant AEG1 expression is correlated with a poor clinical prognosis and chemoresistance in patients with tumors [ 17 – 19 ].…”