Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
FEBS Lett. 2011 Nov 4;585(21):3378-84. doi: 10.1016/j.febslet.2011.09.039. Epub 2011 Oct 5.
Fibronectin (FN) matrix assembly is an essential process in normal vertebrate development, which is frequently lost in tumor cells. Here we show that membrane-type 1 matrix metalloproteinase (MT1-MMP) regulates FN matrix assembly. MT1-MMP knockdown induced FN assembly in breast carcinoma cells. Ectopic expression of MT1-MMP reduced specifically the assembled FN matrix level without affecting whole FN production in fibroblasts. Treatment of fibrosarcoma HT1080 cells with dexamethasone (DEX) enhanced FN synthesis, resulting in short fibrils but not dense matrix formation. Combined treatment of DEX and MT1-MMP inhibitor accelerated FN matrix assembly, which mediated cellular adhesion and reduced cell migration and invasion. These results indicate that MT1-MMP stimulates cell migration and invasion by negatively regulating FN assembly.
纤连蛋白（FN）基质组装是脊椎动物正常发育过程中的一个重要过程，但在肿瘤细胞中经常丢失。在这里，我们发现膜型 1 基质金属蛋白酶（MT1-MMP）调节 FN 基质组装。MT1-MMP 敲低诱导乳腺癌细胞中的 FN 组装。MT1-MMP 的异位表达特异性降低了组装的 FN 基质水平，而不影响成纤维细胞中整个 FN 的产生。地塞米松（DEX）处理纤维肉瘤 HT1080 细胞增强了 FN 的合成，导致短纤维而不是致密基质的形成。DEX 和 MT1-MMP 抑制剂的联合处理加速了 FN 基质的组装，从而介导细胞黏附，减少细胞迁移和侵袭。这些结果表明，MT1-MMP 通过负调控 FN 组装来刺激细胞迁移和侵袭。
