School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
J Biol Chem. 2011 Dec 9;286(49):42072-42081. doi: 10.1074/jbc.M111.272302. Epub 2011 Oct 18.
Extracellular proteolysis mediates tissue homeostasis. In cancer, altered proteolysis leads to abnormal tumor growth, inflammation, tissue invasion, and metastasis. Matrix metalloproteinase-9 (MMP-9) represents one of the most prominent proteinases associated with inflammation and tumorigenesis. The recently identified human transcription factor sLZIP is a member of the leucine zipper transcription factor family. Although sLZIP is known to function in ligand-induced transactivation of the glucocorticoid receptor, its exact functions and target genes are not known. In this study, we investigated the role of sLZIP in MMP-9 expression and its involvement in cervical cancer development. Our results show that sLZIP increased the expression of MMP-9 at both the mRNA and protein levels and the proteolytic activity of MMP-9 in HeLa and SiHa cells. sLZIP also increased the transcriptional activity of MMP-9 by binding directly to the cAMP-responsive element of the MMP-9 promoter region. Involvement of sLZIP in MMP-9 expression was further supported by the fact that ME-180 cells expressing sLZIP siRNA were refractory to MMP-9 expression. Results from wound healing and invasion assays showed that sLZIP enhanced both the migration and invasion of cervical cancer cells. The increased migration and invasion of HeLa and SiHa cells that were induced by sLZIP were abrogated by inhibition of the proteolytic activity of MMP-9. These results indicate that sLZIP plays a critical role in MMP-9 expression and is probably involved in invasion and metastasis of cervical cancer.
细胞外蛋白水解介导组织动态平衡。在癌症中，蛋白水解的改变导致异常的肿瘤生长、炎症、组织侵袭和转移。基质金属蛋白酶-9（MMP-9）是与炎症和肿瘤发生最相关的蛋白水解酶之一。最近发现的人类转录因子 sLZIP 是亮氨酸拉链转录因子家族的成员。尽管 sLZIP 已知在配体诱导的糖皮质激素受体的转录激活中发挥作用，但它的确切功能和靶基因尚不清楚。在这项研究中，我们研究了 sLZIP 在 MMP-9 表达中的作用及其在宫颈癌发展中的参与。我们的结果表明，sLZIP 在 HeLa 和 SiHa 细胞中增加了 MMP-9 的 mRNA 和蛋白质水平以及 MMP-9 的蛋白水解活性。sLZIP 还通过直接结合 MMP-9 启动子区域的 cAMP 反应元件增加了 MMP-9 的转录活性。sLZIP 参与 MMP-9 表达的事实进一步得到证实，即表达 sLZIP siRNA 的 ME-180 细胞对 MMP-9 表达具有抗性。伤口愈合和侵袭试验的结果表明，sLZIP 增强了宫颈癌细胞的迁移和侵袭。sLZIP 诱导的 HeLa 和 SiHa 细胞迁移和侵袭的增加被 MMP-9 蛋白水解活性的抑制所阻断。这些结果表明，sLZIP 在 MMP-9 表达中起关键作用，可能参与宫颈癌的侵袭和转移。
