Involvement of NF-kappaB-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. TNFalpha induced the conversion from the proform of ADAM-17 to its mature form time-dependently. TNFalpha 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, TNFalpha activated a transcription factor NF-kappaB in OSCC cells, while NBD peptide, an NF-kappaB inhibitor, inhibited the ADAM-17 maturation, thus suggesting that NF-kappaB is involved in ADAM-17 maturation. Moreover, an in vitro invasion assay revealed that both ADAM-17 siRNA and NBD peptides strongly suppressed the TNFalpha-induced invasion of OSCC cells through the matrix. In conclusion, ADAM-17 plays an important role in cancer invasion probably through CD44 cleavage.
Takamune
Yasuo
Y
Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Ikebe
Tetsuro
T
Nagano
Osamu
O
Shinohara
Masanori
M
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human