Towards novel anti-cancer strategies based on cystatin function.
Cystatins have recently emerged as important players in a multitude of physiological and patho-physiological settings that range from cell survival and proliferation, to differentiation, cell signaling and immunomodulation. This group of cysteine protease inhibitors forms a large super-family of proteins composed of one, two, three, and, in some species, more than three cystatin domains. Over the last 20 years or so, members of the cystatin super-family have been primarily explored with respect to their capacity to inhibit intracellular cysteine proteases. Yet, this classical mode of action does not fully explain their remarkably diverse biological functions. Due to the space limitations, the author will discuss here the most recent findings that suggest that some of the single-domain, cytoplasmic and cell-secreted cystatins may play important roles in the promotion or suppression of tumor growth, invasion and metastasis. Based on the present understanding of cystatin function, novel avenues for anti-cancer strategies are proposed.
Keppler
Daniel
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Department of Cellular Biology and Anatomy and Feist-Weiller Cancer Center, School of Medicine, Louisiana State University Health Sciences Center in Shreveport, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71130, USA. dkeppl@lsuhsc.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000502:physiology; D055312:Cystatin A; D055313:Cystatin B; D055316:Cystatin C; D055332:Cystatin M; D015891:Cystatins / Q000145:classification / Q000502:physiology* / Q000627:therapeutic use; D015853:Cysteine Proteinase Inhibitors / Q000502:physiology*; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C525030:CST3 protein, human; C525104:CST6 protein, human; C116891:CST7 protein, human; C524994:CSTB protein, human; D055312:Cystatin A; D055316:Cystatin C; D055332:Cystatin M; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D055313:Cystatin B