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


CONCLUSIONS
High expression of AEG-1 is associated with lymph node metastasis and its potentially associated mechanism is investigated.
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan. hcw0928@gate.sinica.edu.tw.
Yi-Ping
YP
Wang
I-Ju
IJ
Liu
Chiung-Pin
CP
Chiang
Han-Chung
HC
Wu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000502:physiology*; D045744:Cell Line, Tumor; D004790:Enzyme Induction; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins; D051996:Transcription Factor RelA / Q000378:metabolism*; D047368:Tumor Burden; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; C498143:RELA protein, human; D016601:RNA-Binding Proteins; D051996:Transcription Factor RelA; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1