Involvement of NF-κB-mediated maturation of ADAM-17 in the invasion of oral squamous cell carcinoma

The involvement of a disintegrin and metalloprotease domain (ADAM)-17 on the cancer invasion was investigated in oral squamous cell carcinoma (OSCC) cells. TNFα induced the conversion from the proform of ADAM-17 to its mature form time-dependently. TNFα also cleaved CD44 to its small fragments, as observed by a Western blot analysis. The transfection of ADAM-17 siRNA partially suppressed the expression of ADAM-17 as well as the cleavage of CD44. On the other hand, TNFα activated a transcription factor NF-κB in OSCC cells, while NBD peptide, an NF-κB inhibitor, inhibited the ADAM-17 maturation, thus suggesting that NF-κB is involved in ADAM-17 maturation. Moreover, an in vitro invasion assay revealed that both ADAM-17 siRNA and NBD peptides strongly suppressed the TNFα-induced invasion of OSCC cells through the matrix. In conclusion, ADAM-17 plays an important role in cancer invasion probably through CD44 cleavage.