AEG-1 may therefore represent a novel genetic biomarker to serve as an attractive molecular target for new anticancer agents to prevent PC cell progression and metastasis.
LYRIC/AEG-1 is a unique protein that has been shown to promote tumor cell migration and invasion through activation of the transcription factor NF-kappaB.
Although pertinent roles of AEG-1 in the carcinogenic process are established, its potential function (promotion of metastasis only versus functioning as a bona fide oncogene) as well as localization (cell surface versus nucleus) remain areas requiring further clarification.
Statistical analysis showed a significant correlation of AEG-1 expression with tumor grade (P <0.001), clinical staging (P = 0.003), T classification (P = 0.003) as well as metastasis classification (P=0.032).
Astrocyte-elevated gene-1 (AEG-1) expression increases in multiple cancers and plays a crucial role in oncogenic transformation and angiogenesis, which are essential components in tumor cell development, growth, and progression to metastasis.
While overexpression of metadherin (MTDH) in breast cancer cell lines and tissues has been found to be associated with aggressive tumor behavior, its precise role in invasion and metastasis is largely unknown.
Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression.
We further found that the positive and specificity predictive value of AEG-1 staining were better for peritoneal metastasis, whereas the negative and sensitivity predictive value of AEG-1 staining were better for lymph node metastasis.
In a nude mice model, the shRNA-mediated downregulation of MTDH resulted in a reduced migratory capacity in HCC cell lines, as well as a reduction in pulmonary and abdominal metastasis.
Dysregulation of miR-375 and MTDH may represent an important oncogenic pathway driving human HNC progression, particularly distant metastases, which is now emerging as a major cause of death for HNC patients.
At the molecular level, we also revealed that the function of astrocyte-elevated gene-1 in promoting metastasis was associated with the activation of matrix metalloproteinase-9 expression.
AEG-1 expression level was correlated with lymph nodal metastasis, histological differentiation, residual tumour size and response to primary chemotherapy.
Considerable evidence suggests that metadherin (MTDH) is a potentially crucial mediator of tumor malignancy and an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk.