Study of Biological Functions of AEG-1/LYRIC in Head and Neck Squamous Cell Carcinoma

• Main Authors: Yi-Ping Wang, 王逸平
• Other Authors: Han-Chung Wu
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/22766610530880814911

博士 === 國立臺灣大學 === 臨床牙醫學研究所 === 102 === 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 HNSCC cell lines and the expression status of AEG-1, phosphorylated p65 and MMP1 are mutually correlated in clinical specimens. Conclusion: High expression of AEG-1 is associated with lymph node metastasis and is a negative prognostic parameter for clinical outcome in HNSCC. Keywords: Astrocyte elevated gene-1 (AEG-1), head and neck squamous cell carcinoma (HNSCC), metastasis, matrix metalloproteinase 1 (MMP1), p65