Cystatins as regulators of cancer

Abstract

The cystatins, natural inhibitors of cysteine proteases, act as metastasis suppressors for a wide variety of different cancers. An update of the various actions of cystatins in cancer is the focus of the current review. In the progression of cancer cells, besides certain genetic changes, augmentation of invasion occurs with an increase in cysteine protease (cathepsin) activity. Because the cystatins are key regulators of the cathepsins, they too play critical roles in cancer. All aspects of metastasis are influenced by the cystatins in a variety of cancers. For some cancers cystatins can be used as prognostic factors. New roles of the cystatins in cancer as gene regulatory proteins are being advanced. Overexpression of cystatins has been found to inhibit metastasis and angiogenesis in certain cancers. The cystatins may introduce future therapeutic advances in the control of cancer.