The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review.
The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review.
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DOI：
10.3390/genes12020308
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发表时间：
2021-02-22
期刊：
影响因子：
3.5
通讯作者：
Sarkar D
中科院分区：
文献类型：
--
作者：
Khan M;Sarkar D
自2002年首次克隆以来，对大量癌症适应症的大量研究有力地证明了AEG-1是一个真正的癌基因。在所有类型的癌细胞中，过表达和敲除研究表明，AEG-1通过多种机制在调节肿瘤细胞的增殖、侵袭、血管生成、转移和化疗耐药方面发挥重要作用，包括激活多种致癌途径的蛋白质相互作用，促进炎症、脂质代谢和肿瘤微环境的翻译和调节的RNA结合。这些发现得到了组织特异性AEG-1转基因小鼠模型肿瘤形成增加的证明，以及对多种类型癌症发展和进展的深刻抵抗，完全和有条件的AEG-1基因敲除小鼠模型。此外，AEG-1在多种癌症中表达的临床病理相关性建立了AEG-1作为高度侵袭性、化疗耐药的转移性疾病和预后不良的独立生物标志物的基础，为机制和小鼠模型研究提供了坚实的基础。在这篇综述中，我们对当前和最新的文献进行了全面的分析，以描述AEG-1在癌症中的临床意义，强调了这些发现的共性和差异，并讨论了这些观察结果的意义。
Since its initial cloning in 2002, a plethora of studies in a vast number of cancer indications, has strongly established AEG-1 as a bona fide oncogene. In all types of cancer cells, overexpression and knockdown studies have demonstrated that AEG-1 performs a seminal role in regulating proliferation, invasion, angiogenesis, metastasis and chemoresistance, the defining cancer hallmarks, by a variety of mechanisms, including protein-protein interactions activating diverse oncogenic pathways, RNA-binding promoting translation and regulation of inflammation, lipid metabolism and tumor microenvironment. These findings have been strongly buttressed by demonstration of increased tumorigenesis in tissue-specific AEG-1 transgenic mouse models, and profound resistance of multiple types of cancer development and progression in total and conditional AEG-1 knockout mouse models. Additionally, clinicopathologic correlations of AEG-1 expression in a diverse array of cancers establishing AEG-1 as an independent biomarker for highly aggressive, chemoresistance metastatic disease with poor prognosis have provided a solid foundation to the mechanistic and mouse model studies. In this review a comprehensive analysis of the current and up-to-date literature is provided to delineate the clinical significance of AEG-1 in cancer highlighting the commonality of the findings and the discrepancies and discussing the implications of these observations.
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