Sinpitaksakul Sariya Nuchanardpanit, Pimkhaokham Atiphan, Sanchavanakit Neeracha, Pavasant Prasit
Graduate program in Oral Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Biochem Biophys Res Commun. 2008 Jul 11;371(4):713-8. doi: 10.1016/j.bbrc.2008.04.128. Epub 2008 May 5.
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.
基质金属蛋白酶-9（MMP-9）通过降解细胞外基质和基底膜在癌症进展中发挥作用。许多生长因子，包括转化生长因子-β1（TGF-β1），都能诱导MMP-9表达。我们证明，TGF-β1可诱导人头颈部鳞状细胞癌细胞系中MMP-9的mRNA和蛋白表达。应用I型TGF-β受体抑制剂（SB505124）可显著降低MMP-9表达。同时，肌球蛋白轻链激酶（MLCK）抑制剂可降低上清液和细胞裂解物中分泌的MMP-9水平，但不能降低MMP-9 mRNA水平。这些结果表明，MLCK可能在转录后调节MMP-9表达。应用SB505124和siRNA Smad2/3可降低肌球蛋白轻链（MLC）磷酸化，提示MLC位于TβRI/Smad2/3信号通路下游。总之，这些结果描述了一种新的机制，即TGF-β1信号通过Smad和MLCK增强诱导MMP-9表达。
