Table 2.

Impact of Glypican 3 on tumorigenesis mechanisms in HCC

Mechanism	Effect on HCC	Key interactions/outcomes	References
Recruitment of TAMs	↑ HCC progression	GPC-3 overexpression reactivates macrophage recruiting ↑ Association with poor prognosis	[22, 31–33]
Glucose metabolism	↑Liver carcinogenesis ↑Metastasis	GPC-3 reprograms metabolism favoring glucose absorption and lactate synthesis acts as a Warburg effect regulator	[36, 37]
EMT	↑Correlation with metastasis	GPC-3 elevation linked to EMT via ERK signaling; ↓ E-cadherins ↑Invasion, ↑metastasis	[10, 39–43]
CXCL12/CXCR4 axis	↑Cellular migration ↑Angiogenesis	↑CXCL12/CXCR4 signaling ↑HCC cell proliferation and migration	[20, 44–46]
Bax/Bcl-2 Pathway	↑Apoptosis resistance	↓Bax/Bcl-2 ↑Cell survival	[47]
SULF-2 interaction	↑Oncogenic effect	↑SULF-2 expression ↑Proliferation ↓Apoptosis	[48–51]

TAMs tumor-associated macrophages, GPC-3 Glypican 3, HCC hepatocellular carcinoma, EMT epithelial–mesenchymal transition, ERK extracellular receptor kinase, CXCL12 C-X-C motif chemokine ligand 12, CXCR4 C-X-C chemokine receptor type 4, SULF-2 sulfatase 2. Symbol: ↑increase, ↓decrease