TGF-beta1 induced MMP-9 expression in HNSCC cell lines via Smad/MLCK pathway.
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.
Sinpitaksakul
Sariya Nuchanardpanit
SN
Graduate program in Oral Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Pimkhaokham
Atiphan
A
Sanchavanakit
Neeracha
N
Pavasant
Prasit
P
D052117:Benzodioxoles / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000032:analysis / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
C519132:2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride; D052117:Benzodioxoles; D007093:Imidazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D009219:Myosin-Light-Chain Kinase; D020780:Matrix Metalloproteinase 9