Abstract
BackgroundThe 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.ResultsHigh 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.ConclusionHigh expression of AEG-1 is associated with lymph node metastasis and its potentially associated mechanism is investigated.
Highlights
The survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities
We report that astrocyte elevated gene-1 (AEG-1) is overexpressed in a majority of clinical specimens of oral squamous cell carcinoma (OSCC, a subset of Head and neck squamous cell carcinoma (HNSCC)), and its expression is positively associated with both the presence and the degree of lymph node metastasis
High AEG-1 expression in OSCC is associated with regional lymph node metastasis and unfavorable 5-year survival Immunohistochemical analysis of AEG-1 revealed high expression of AEG-1 in 40.86% (38 out of 93) of examined OSCC clinical specimens
Summary
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. Astrocyte elevated gene-1 (AEG-1), known as metadherin (MTDH) or LYsine-RIch CEACAM1 coisolated (LYRIC), is a 582 amino acid residues type II transmembrane protein without any known functional domains. It has emerged as a novel oncoprotein essential for malignant progression in various types of human cancers [6,7,8,9,10,11,12,13]. Since the presence of metastatic lesions has a negative impact on the prognosis and morbidity of HNSCC patients, it prompts us to investigate the biological role of AEG-1 in this disease entity
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