The multifaceted role of MTDH/AEG-1 in cancer progression.
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, nuclear factor kappaB (NFkappaB), and Wnt/beta-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.
Hu
Guohong
G
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Wei
Yong
Y
Kang
Yibin
Y
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016601:RNA-Binding Proteins
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; C483038:Mtdh protein, mouse; D016601:RNA-Binding Proteins