解析磷脂酰肌醇蛋白聚糖-3：从结构到病理生理作用及机制——综合视角

Piao Qianling, Bian Xiaona, Zhao Qi, Sun Luguo

National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China.

Cells. 2025 May 15;14(10):726. doi: 10.3390/cells14100726.

(), initially cloned from rats 40 years ago, deeply participates in the development and homeostasis of multiple tissues and organs. Dysregulation of GPC3 is associated with cancerous and noncancerous diseases. Loss of the function of GPC3 leads to Simpson-Golabi-Behmel syndrome (SGBS), which is characterized by pre- and postnatal overgrowth. However, GPC3 exerts both promotive and inhibitory roles in cancer development. Recent studies suggest that the dual roles of GPC3 in cancer may be attributed to its structural features. This review comprehensively summarizes the structural features, pathophysiological functions, and underlying mechanism of GPC3 and finally discuss the relationship between its structural modification and functions, aiming to provide a theoretical basis for the development of novel therapeutic strategies targeting GPC3 to treat diseases including cancer.

GPC3于40年前最初从大鼠中克隆出来，深度参与多种组织和器官的发育及内稳态维持。GPC3失调与癌症及非癌症疾病相关。GPC3功能丧失导致辛普森-戈拉比-贝梅尔综合征（SGBS），其特征为出生前后过度生长。然而，GPC3在癌症发展中发挥促进和抑制双重作用。近期研究表明，GPC3在癌症中的双重作用可能归因于其结构特征。本综述全面总结了GPC3的结构特征、病理生理功能及潜在机制，最后讨论了其结构修饰与功能之间的关系，旨在为开发以GPC3为靶点治疗包括癌症在内的疾病的新型治疗策略提供理论依据。