Unraveling Glypican-3: From Structural to Pathophysiological Roles and Mechanisms-An Integrative Perspective.

Glypican3 (GPC3), 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.