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Trends Cell Biol. 2011 Apr;21(4):228-37. doi: 10.1016/j.tcb.2010.12.002. Epub 2011 Jan 12.

Proteolytic networks in cancer.

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  • 1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Abstract

Proteases are important for multiple processes during malignant progression, including tumor angiogenesis, invasion and metastasis. Recent evidence reveals that tumor-promoting proteases function as part of an extensive multidirectional network of proteolytic interactions, in contrast to the unidirectional caspase cascade. These networks involve different constituents of the tumor microenvironment and key proteases, such as cathepsin B, urokinase-type plasminogen activator and several matrix metalloproteinases, occupy central nodes for amplifying proteolytic signals passing through the network. The proteolytic network interacts with other important signaling pathways in tumor biology, involving chemokines, cytokines, and kinases. Viewing these proteolytic interactions as a system of activating and inhibiting reactions provides insight into tumor biology and reveals relevant pharmaceutical targets. This review examines recent advances in understanding proteases in cancer and summarizes how the network of activity is co-opted to promote tumor progression.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID:
21232958
[PubMed - indexed for MEDLINE]
PMCID:
PMC3840715
Free PMC Article
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