Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
School of Life Sciences, East China Normal University, Shanghai, China.
Am J Physiol Cell Physiol. 2021 Nov 1;321(5):C846-C858. doi: 10.1152/ajpcell.00290.2021. Epub 2021 Sep 22.
Glypican-1 (GPC1) is one of the six glypican family members in humans. It is composed of a core protein with three heparan sulfate chains and attached to the cell membrane by a glycosyl-phosphatidylinositol anchor. GPC1 modulates various signaling pathways including fibroblast growth factors (FGF), vascular endothelial growth factor-A (VEGF-A), transforming growth factor-β (TGF-β), Wnt, Hedgehog (Hh), and bone morphogenic protein (BMP) through specific interactions with pathway ligands and receptors. The impact of these interactions on signaling pathways, activating or inhibitory, is dependent upon specific GPC1 domain interaction with pathway components, as well as cell surface context. In this review, we summarize the current understanding of the structure of GPC1, as well as its role in regulating multiple signaling pathways. We focus on the functions of GPC1 in cancer cells and how new insights into these signaling processes can inform its translational potential as a therapeutic target in cancer.
Glypican-1（GPC1）是人类六种 Glypican 家族成员之一。它由一个核心蛋白组成，带有三条肝素硫酸链，并通过糖基磷脂酰肌醇锚附着在细胞膜上。GPC1 通过与途径配体和受体的特异性相互作用，调节包括成纤维细胞生长因子（FGF）、血管内皮生长因子-A（VEGF-A）、转化生长因子-β（TGF-β）、Wnt、Hedgehog（Hh）和骨形态发生蛋白（BMP）在内的各种信号通路。这些相互作用对信号通路的影响是激活还是抑制，取决于 GPC1 结构域与途径成分的特异性相互作用，以及细胞表面环境。在这篇综述中，我们总结了 GPC1 的结构及其在调节多种信号通路中的作用。我们重点介绍了 GPC1 在癌细胞中的功能，以及对这些信号过程的新认识如何为其作为癌症治疗靶点的转化潜力提供信息。
