Structural and functional impact of post-translation modification of GPC3 on liver carcinogenesis.

Glypican-3 (GPC3) is a cell-surface glycoprotein that is frequently overexpressed in hepatocellular carcinoma. GPC3 undergoes extensive post-translational modification including cleavage and glycosylation. This review focuses on the structure and function of GPC3 in liver cancer, highlighting the post-translation modification (PTM) of the tertiary and quaternary structures of GPC3 as a potential oncogenic regulatory mechanism. We propose that the function of GPC3 in normal development can vary with extensive PTM and that dysregulation of these processes leads to disease. Defining the regulatory impact of these modifications can provide a deeper understanding of the role of GPC3 in oncogenesis, epithelial-mesenchymal transition, and drug development. Through review of current literature, this paper provides a unique perspective on the role of GPC3 in liver cancer, focusing on potential regulatory mechanisms of post-translational modifications on GPC3 function at the molecular, cellular, and disease level.