As far as we know, this is the first study to demonstrate that AEG-1 modulates the phosphorylation at serine 536 of the p65 subunit of NF-κB in HNSCC, which in turn regulates the production of MMP1 by manipulating the binding of NF-κB to its promoter region. Here, RELA is linked to head and neck squamous cell carcinoma.