Journal
FEBS JOURNAL
Volume 280, Issue 10, Pages 2294-2306Publisher
WILEY
DOI: 10.1111/febs.12168
Keywords
extracellular signal-regulated kinase; heparan sulfate; heparanase; heparin mimics; hepatocyte growth factor; syndecan-1; vascular endothelial growth factor
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Funding
- NIH [CA135075, CA138340, CA138535]
- United States-Israel Binational Science Foundation [2009230]
- Division Of Astronomical Sciences
- Direct For Mathematical & Physical Scien [2009230] Funding Source: National Science Foundation
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Heparanase is an endoglucuronidase that cleaves heparan sulfate chains of proteoglycans. In many malignancies, high heparanase expression and activity correlate with an aggressive tumour phenotype. A major consequence of heparanase action in cancer is a robust up-regulation of growth factor expression and increased shedding of syndecan-1 (a transmembrane heparan sulfate proteoglycan). Substantial evidence indicates that heparanase and syndecan-1 work together to drive growth factor signalling and regulate cell behaviours that enhance tumour growth, dissemination, angiogenesis and osteolysis. Preclinical and clinical studies have demonstrated that therapies targeting the heparanase/syndecan-1 axis hold promise for blocking the aggressive behaviour of cancer.
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