TGF-β1 induced MMP-9 expression in HNSCC cell lines via Smad/MLCK pathway

• DOI: 10.1016/j.bbrc.2008.04.128
• Publication Date: 2008-05-06T18:02:58Z
• Authors: Sariya Nuchanardp...; Atiphan Pimkhaokham; Neeracha Sanchava...; Prasit Pavasant
• Keywords: 0301 basic medicine; Pyridines; Imidazoles; 3. Good health; Transforming Growth Factor beta1; 03 medical and health sciences; Matrix Metalloproteinase 9; Head and Neck Neoplasms; Cell Line, Tumor; Carcinoma, Squamous Cell; Humans; Benzodioxoles; Smad3 Protein; RNA, Small Interfering; Myosin-Light-Chain Kinase; Receptors, Transforming Growth Factor beta

Matrix metalloproteinase-9 (MMP-9) plays roles in cancer progression by degrading the extracellular matrix and basement membrane. Many growth factors including Transforming growth factor-beta1 (TGF-beta1) could induce MMP-9 expression. We demonstrated that TGF-beta1 induced MMP-9 mRNA and protein in human head and neck squamous cell carcinoma cell lines. Application of TGF-beta receptor type I inhibitor (SB505124) reduced the MMP-9 expression markedly. Whilst, inhibitor of Myosin light chain kinase (MLCK) could reduce the level of secreted MMP-9 in both the supernatants and cell lysate but not the level of MMP-9 mRNA. These suggested that MLCK might regulate MMP-9 expression post-transcriptionally. Application of SB505124 and siRNA Smad2/3 reduced the phosphorylation of myosin light chain (MLC) suggested that MLC is downstream to TbetaRI/Smad2/3 signaling pathway. In conclusion, these results describe a novel mechanism for the potentiation of TGF-beta1 signaling to induce MMP-9 expression via Smad and MLCK.