Regulation of MMP-9 gene expression for the development of novel molecular targets against cancer and inflammatory diseases

Abstract

The need to pharmacologically control the proteolytic activity of matrix metalloproteinases (MMPs) has been commonly acknowledged, despite its limited efficacy in clinical trials. Among the reasons that explain this failure is our limited understanding of the signals that control the expression of MMPs in different cell types during different pathological conditions. Thus, future therapies must rely on more selective approaches. With the continually increasing body of proof implicating MMPs in a large number of diseases, it has become a priority to establish the pertinence of molecules involved in the signalling pathways leading to the expression of these enzymes. MMP-9 is a case in point: its dramatic overexpression in cancer and various inflammatory conditions clearly points to the molecular mechanisms controlling its expression as a potential target for eventual rational therapeutic intervention. In this article, recent progress in the signalling pathways that regulate MMP-9 expression is reviewed, and the latest strategies to be considered in the search for a specific inhibitor of its expression are presented.

• cancer
• DNA methylation
• gene transcription
• inflammatory cytokines
• inflammatory mediators
• matrix metalloproteinase (MMP)-9
• PKC