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_Cancer Research Journal - This journal ceased publication after 4#4 (2010). Back Issues are available.
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Cystatins in Human Cancer pp. 225-238 $100.00
Authors:  (Mysore S. Veena, Eri S. Srivatsan, Department of Surgery, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, California, USA)
Abstract:
Cystatins are protease inhibitors that are specifically active against lysosomal cysteine proteases. Cystatins regulate proteases by the formation of reversible high affinity complexes. Members of this superfamily are classified into three subfamilies based on their amino acid homology 1) Type 1 cystatins (cystatin A and B) have a single cystatin domain, intracellular, and lack secretory signal, 2) type 2 cystatins are mainly secretory and comprised of cystatin C, D, E/M, F, S, SN, and SA, 3) type 3 cystatins are those with multi cystatin domains and represent kininogens, the plasma proteins.
Cystatins are essential to maintain cell homeostasis. Impairment of cystatins and their substrate proteases leads to pathological conditions including cancer. While some of the cystatins are over-expressed in some cancers they are also down-regulated. Cystatin A is over-expressed in lung, breast, head and neck and prostate cancers and serves as an important prognostic biomarker. Cystatin B expression is elevated in lung, breast, prostate, and hepatocellular carcinoma while being down regulated in oesophageal cancer. In contrast to Type 1 cystatins, Type 2 cystatins are mostly down regulated in breast, lung, cervical, prostate, and brain cancers. Type 2 cystatins are inactivated by various mechanisms including deletion, promoter hypermethylaion, deacetylation, and mutations in the substrate binding regions. Type 3 cystatins, kininogens, have been
shown to play a suppressive role in colon cancer. The functions of cystatins in different cancers are not limited to protease inhibition alone but also include cell cycle regulation, apoptosis, and cancer cell adhesion. In this chapter, details on the mechanisms of cystatin
gene inactivation and their role in different cancers are summarized. 


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Cystatins in Human Cancer pp. 225-238