The multifaceted role of MTDH/AEG-1 in cancer progression.
The multifaceted role of MTDH/AEG-1 in cancer progression.
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DOI：
10.1158/1078-0432.ccr-09-0049
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发表时间：
2009-09-15
期刊：
影响因子：
--
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
Hu G;Wei Y;Kang Y
癌症是通过遗传或表观遗传改变的积累而逐渐获得多种恶性特征的结果。最近的研究已经确定了MTDH（Metadherin）/AEG-1（Astrocyte Elevated Gene 1）在肿瘤进展的几个关键方面的功能作用，包括转化、凋亡逃避、侵袭、转移和化学抗性。MTDH/AEG-1的过表达经常在黑色素瘤、神经胶质瘤、神经母细胞瘤以及乳腺癌、前列腺癌、肝癌和食道癌中观察到，并且与不良的临床结果相关。MTDH/AEG-1作为致癌Ha-Ras和c-Myc转化活性的下游介导剂发挥作用。此外，MTDH/AEG-1过表达激活PI 3 K/Akt、NFκB和Wnt/β-catenin信号通路以刺激增殖、侵袭、细胞存活和化学抗性。MTDH/AEG-1的肺归巢结构域还介导肿瘤细胞粘附到远处器官的脉管系统并促进转移。这些发现表明，MTDH/AEG-1的治疗靶向可以同时抑制肿瘤生长、阻断转移并增强化学治疗的功效。
Cancer is the result of the progressive acquisition of multiple malignant traits through the accumulation of genetic or epigenetic alterations. Recent studies have established a functional role of MTDH (Metadherin)/AEG-1 (Astrocyte Elevated Gene 1) in several crucial aspects of tumor progression, including transformation, evasion of apoptosis, invasion, metastasis and chemoresistance. Overexpression of MTDH/AEG-1 is frequently observed in melanoma, glioma, neuroblastoma, and carcinomas of breast, prostate, liver and esophagus and is correlated with poor clinical outcomes. MTDH/AEG-1 functions as a downstream mediator of the transforming activity of oncogenic Ha-Ras and c-Myc. Furthermore, MTDH/AEG-1 overexpression activates the PI3K/Akt, NFκB, and Wnt/β-catenin signaling pathways to stimulate proliferation, invasion, cell survival and chemoresistance. The lung-homing domain of MTDH/AEG-1 also mediates the adhesion of tumor cells to the vasculature of distant organs and promotes metastasis. These findings suggest that therapeutic targeting of MTDH/AEG-1 may simultaneously suppress tumor growth, block metastasis and enhance the efficacy of chemotherapeutic treatments.