期刊
TRENDS IN BIOCHEMICAL SCIENCES
卷 39, 期 6, 页码 277-288出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tibs.2014.03.001
关键词
heparin; heparan sulfate; metastasis; sulfyltransferase; sulfatase; heparanase
资金
- National Institutes of Health (NIH) [F30 CA168043-01, R01-CA136786, R01-CA135006]
- Alex's Lemonade Stand
Heparan sulfate (HS) is a biopolymer consisting of variably sulfated repeating disaccharide units. The anticoagulant heparin is a highly sulfated intracellular variant of HS. HS has demonstrated roles in embryonic development, homeostasis, and human disease via non-covalent interactions with numerous cellular proteins, including growth factors and their receptors. HS can function as a co-receptor by enhancing receptor-complex formation. In other contexts, HS disrupts signaling complexes or serves as a ligand sink. The effects of HS on growth factor signaling are tightly regulated by the actions of sulfyltransferases, sulfatases, and heparanases. HS has important emerging roles in oncogenesis, and heparin derivatives represent potential therapeutic strategies for human cancers. Here we review recent insights into HS signaling in tumor proliferation, angiogenesis, metastasis, and differentiation. A cancer-specific understanding of HS signaling could uncover potential therapeutic targets in this highly actionable signaling network.
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