The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review

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.