In mammalian cells, cysteine proteinases are localized mainly in the cytoplasm and lysosomal compartments. For lysosomal cysteine proteinases, they are synthesized as inactive zymogens and converted to active forms occurred in the acidic and reducing conditions of late endosomes or lysosomes. Here we review the roles of active lysosomal cysteine proteinases in particular cathepsin S and its importance to many physiological or pathological processes including tumor growth, angiogenesis, and metastasis. Biochemical and clinical studies have shown significant changes in the levels of mRNA expression and enzyme activity of cathepsin S in various cancer tissues and cell lines. Immunologic, molecular and pharmaceutical approaches to alter the expression and proteolytic activity of cathepsin S all provided strong evidence for a causal role of this proteolytic enzyme in tumor progression and invasion. Determination of the X-ray structures of either cathepsin S alone or complexed with inhibitors further offered insights of the active site pocket of cathepsin S, thereby making the rational design of low-molecular weight synthetic inhibitors feasible for anti-cancer drug development and treatment.
Date:
2007-02-17
Relation:
Journal of Cancer Molecules. 2007 Feb 17;3(1):5-14.
