Overexpression of astrocyte-elevated gene-1 is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through up-regulation of matrix metalloproteinase-9 expression

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• 作者：Shijun Sun ; PhD^a ; ¹ ; Zunfu Ke ; PhD^a ; ¹ ; ^{kezunfu@126.com} ; Fen Wang ; MD^a ; Shuhua Li ; MD^a ; Wenfang Chen ; PhD^a ; Anjia Han ; PhD^a ; Zuo Wang ; MD^a ; Huijuan Shi ; MD^a ; Lian-tang Wang ; PhD^a ; Xiaodong Chen ; MD^b
• 关键词：AEG-1 ; Lung cancer ; MMP-2 ; MMP-9 ; Metastasis
• 刊名：Human Pathology
• 出版年：2012
• 期刊代码：140_00468177
• 类别：med
• 出版时间：July, 2012
• 卷：43
• 期：7
• 页码：1051-1060
• 文件大小：2268 K

摘要

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Summary

Expression of astrocyte-elevated gene-1, a novel oncoprotein, is elevated in multiple cancers and plays a vital role in tumor cell growth, invasion, angiogenesis, and progression to metastasis. However, the functional significance of astrocyte-elevated gene-1 in non-small cell lung cancer still remains unclear. Our present study showed that the markedly up-regulated expression of astrocyte-elevated gene-1 was observed in non-small cell lung cancer cell lines and tissues at the level of both transcription and translation. Simultaneously, ectopic expression or small interfering RNA silencing of astrocyte-elevated gene-1 markedly enhanced or inhibited the invasive ability of non-small cell lung cancer cells, respectively. At the molecular level, we also revealed that the function of astrocyte-elevated gene-1 in promoting metastasis was associated with the activation of matrix metalloproteinase-9 expression. Consistent with these observations, immunostaining analysis revealed a significant positive correlation between astrocyte-elevated gene-1 and matrix metalloproteinase-9. Moreover, subcutaneous xenografts of non-small cell lung cancer cells engineered to express astrocyte-elevated gene-1 were highly invasive compared with the parental cells and expressed a high level of matrix metalloproteinase-9. In archival non-small cell lung cancer specimens, high astrocyte-elevated gene-1 expression correlated significantly with clinical staging (P = .048), differentiation (P = .023), and lymph node metastasis (P = .032). The overall survival time in patients with high astrocyte-elevated gene-1 expression was notably shorter than that in patients with low astrocyte-elevated gene-1 expression (P < .001). Taken together, our results indicate that astrocyte-elevated gene-1 plays a crucial role in the carcinogenesis and aggressiveness of non-small cell lung cancer, promoting its metastasis by modulating matrix metalloproteinase-9 expression and leading to a poor clinical prognosis.