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

Molecular Cancer

Research

Chiung-Pin Chiang¹  Yi-Ping Wang²  I-Ju Liu³  Han-Chung Wu⁴ 

[1]Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan

[2]Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan

[3]Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan

[4]Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

[5]Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan

[6]Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

[7]Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

[8]Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan

关键词: Astrocyte elevated gene-1 (AEG-1);    Head and neck squamous cell carcinoma (HNSCC);    Metastasis;    Matrix metalloproteinase 1 (MMP1);    p65;   

DOI  :  10.1186/1476-4598-12-109

 received in 2013-07-03, accepted in 2013-09-17,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Wang et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.