Kolluri Aarti, Ho Mitchell
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, United States.
Front Oncol. 2019 Aug 2;9:708. doi: 10.3389/fonc.2019.00708. eCollection 2019.
Glypican-3 (GPC3) is a cell-surface glycoprotein consisting of heparan sulfate glycosaminoglycan chains and an inner protein core. It has important functions in cellular signaling including cell growth, embryogenesis, and differentiation. GPC3 has been linked to hepatocellular carcinoma and a few other cancers, however, the mechanistic role of GPC3 in cancer development remains elusive. Recent breakthroughs including the structural modeling of GPC3 and GPC3-Wnt complexes represent important steps toward deciphering the molecular mechanism of action for GPC3 and how it may regulate cancer signaling and tumor growth. A full understanding of the molecular basis of GPC3-mediated signaling requires elucidation of the dynamics of partner receptors, transducer complexes, and downstream players. Herein, we summarize current insights into the role of GPC3 in regulating cancer development through Wnt and other signaling pathways, including YAP and hedgehog cascades. We also highlight the growing body of work which underlies deciphering how GPC3 is a key player in liver oncogenesis.
磷脂酰肌醇蛋白聚糖-3（GPC3）是一种细胞表面糖蛋白，由硫酸乙酰肝素糖胺聚糖链和一个内部蛋白质核心组成。它在包括细胞生长、胚胎发生和分化在内的细胞信号传导中具有重要功能。GPC3与肝细胞癌和其他一些癌症有关，然而，GPC3在癌症发展中的机制作用仍不清楚。最近的突破，包括GPC3和GPC3-Wnt复合物的结构建模，代表了朝着破译GPC3的分子作用机制以及它如何调节癌症信号传导和肿瘤生长迈出的重要一步。对GPC3介导的信号传导的分子基础的全面理解需要阐明伙伴受体、转导复合物和下游参与者的动态变化。在此，我们总结了目前对GPC3通过Wnt和其他信号通路（包括YAP和刺猬信号通路）调节癌症发展作用的见解。我们还强调了越来越多的研究工作，这些工作为破译GPC3如何成为肝脏肿瘤发生的关键因素奠定了基础。
