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 transcription factor human 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 showed that sLZIP increased the expression of MMP-9 at both the mRNA and the protein levels, and the proteolytic activity of MMP-9 in HeLa and SiHa cells. sLZIP also increased the transcription activity of MMP-9 by binding directly to the CRE 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 is induced by sLZIP were abrogated by inhibition of the proteolytic activity of MMP-9. These results indicate that sLZIP plays a critical role in expression of MMP-9 and is probably involved in invasion and metastasis of cervical cancer.

PMID: 22009750 [PubMed - as supplied by publisher] Source: National Library of Medicine. Free full text