Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis

Abstract

Astrocyte elevated gene-1 (AEG-1), upregulated in various types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, the functional significance of AEG-1 in human esophageal squamous cell carcinoma (ESCC) remains unknown. In the present study, we showed the expression of AEG-1 was markedly upregulated in esophageal cancer cell lines and surgical ESCC specimens at both transcriptional and translational levels. Immunohistochemical analysis revealed that 80 of 168 (47.6%) paraffin-embedded archival ESCC specimens exhibited high levels of AEG-1 expression. Statistical analysis suggested the upregulation of AEG-1 was significantly correlated with the clinical staging of the ESCC patients (P 5 0.001), T classification (P 5 0.002), N classification (P 5 0.034), M classification (P 5 0.021) and histological differentiation (P 5 0.035) and those patients with high AEG-1 levels exhibited shorter survival time (P < 0.001). Multivariate analysis indicated that AEG-1 expression might be an independent prognostic indicator of the survival of patients with ESCC. Furthermore, we found that ectopic expression of AEG-1 in ESCC cells could significantly enhance cell proliferation and anchorage-independent growth ability. Conversely, silencing AEG-1 by short hairpin RNAi caused an inhibition of cell growth and anchorage-independent growth ability on soft agar. Moreover, we demonstrated that the upregulation of AEG-1 could reduce the expression of p27 Kip1 and induce the expression of cyclin D1 through the AKT/FOXO3a pathway. Our findings suggest that the AEG-1 protein is a valuable marker of ESCC progression and that the upregulation of AEG-1 plays an important role in the development and pathogenesis of human ESCC.

Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC)

“…32 Overexpression of AEG-1/MTDH was observed in many types of cancers, such as malignant astrocytoma, 33 neuroblastoma, 34 and cancers of esophagus, 35 breast, 36 prostate 37 and liver. 38 Many reports have indicated that AEG-1/MTDH contributes to several steps in human oncogenesis, including cancer-cell progression, invasion, metastasis and chemoresistance.…”

MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo

“…Overexpression of AEG-1 was observed in melanoma (Kang et al, 2005), glioma (Kang et al, 2005), neuroblastoma (Lee et al, 2009), and carcinomas of breast (Li et al, 2008), prostate (Kikuno et al, 2007), esophagus (Yu et al, 2009), stomach (Jian-bo et al, 2011 and liver (Yoo et al, 2009), which was correlated with poor clinical outcomes. It was reported that AEG-1 was overexpressed in 490% of human HCC compared with normal liver and had a central role in regulating diverse aspects of HCC pathogenesis (Yoo et al, 2009).…”

Metadherin regulates radioresistance in cervical cancer cells

“…Recently, clinical studies have revealed that MTDH is overexpressed in various malignancies, including breast, prostate, glioma, hepatocellular, and esophageal cancer and is associated with disease progression and poor clinical outcomes (14). Moreover, MTDH has been found to promote cancer metastasis, chemoresistance, invasion and angiogenesis (15)(16)(17)(18)(19)(20)(21), suggesting that it may function as an oncogene. Furthermore, MTDH knockdown has been found to sensitize breast cancer and neuroblastoma cells to cisplatin (15,17).…”