Knelson Erik H, Nee Jasmine C, Blobe Gerard C
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA; Medical Scientist Training Program, Duke University Medical Center, Durham, NC, USA.
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Trends Biochem Sci. 2014 Jun;39(6):277-88. doi: 10.1016/j.tibs.2014.03.001. Epub 2014 Apr 19.
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.
硫酸乙酰肝素（HS）是一种由可变硫酸化的重复二糖单元组成的生物聚合物。抗凝剂肝素是HS的一种高度硫酸化的细胞内变体。HS已通过与多种细胞蛋白（包括生长因子及其受体）的非共价相互作用，在胚胎发育、体内平衡和人类疾病中发挥作用。HS可通过增强受体复合物的形成作为共受体。在其他情况下，HS会破坏信号复合物或充当配体库。HS对生长因子信号传导的影响受到硫酸转移酶、硫酸酯酶和乙酰肝素酶作用的严格调控。HS在肿瘤发生中具有重要的新作用，肝素衍生物代表了人类癌症的潜在治疗策略。在这里，我们综述了关于HS在肿瘤增殖、血管生成、转移和分化中的信号传导的最新见解。对HS信号传导的癌症特异性理解可能会揭示这个高度可行的信号网络中的潜在治疗靶点。
