title: Heparan sulfate signaling in cancer.
abstract: 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.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA; Medical Scientist Training Program, Duke University Medical Center, Durham, NC, USA.
authors.forename: Erik H
authors.initials: EH
authors.lastname: Knelson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Jasmine C
authors.initials: JC
authors.lastname: Nee
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA; Department of Medicine, Duke University Medical Center, Durham, NC, USA. Electronic address: gerard.blobe@duke.edu.
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Blobe
mesh_terms: D000818:Animals; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D006497:Heparan Sulfate
keywords: heparan sulfate; heparanase; heparin; metastasis; sulfatase; sulfyltransferase
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