Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1.

Abstract:

BACKGROUND:The survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1), a single transmembrane protein without any known functional domains, is overexpressed in various malignancies and is implicated in both distant metastasis and poor survival. RESULTS:High expression of AEG-1 in HNSCC was positively correlated with regional lymph node metastasis and a poor 5-year survival rate. Knockdown of AEG-1 in HNSCC cell lines reduced their capacity for colony formation, migration and invasion. Furthermore, decreased tumor volume and metastatic foci were observed after knockdown of AEG-1 in subcutaneous xenografts and pulmonary metastasis assays in vivo, respectively. We also demonstrated that AEG-1 increased phosphorylation of the p65 subunit of NF-κB, and regulated the expression of MMP1 in HNSCC cells. Moreover, compromised phosphorylation of the p65 (RelA) subunit of NF-κB at serine 536 was observed upon silencing of AEG-1 in both HNSCC cell lines and clinical specimens. CONCLUSION:High expression of AEG-1 is associated with lymph node metastasis and its potentially associated mechanism is investigated.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Wang YP,Liu IJ,Chiang CP,Wu HC

doi

10.1186/1476-4598-12-109

subject

Has Abstract

pub_date

2013-09-24 00:00:00

pages

109

issue

1

issn

1476-4598

pii

1476-4598-12-109

journal_volume

12

pub_type

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