The multifaceted role of MTDH/AEG-1 in cancer progression

Guohong Hu, Yong Wei, Yibin Kang

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

Abstract

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 κB(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.

Original languageEnglish (US)
Pages (from-to)5615-5620
Number of pages6
JournalClinical Cancer Research
Volume15
Issue number18
DOIs
StatePublished - Sep 15 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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