The GPC1 Knockout SK-HEP-1 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human hepatocellular carcinoma line, with targeted disruption of the glypican-1 (GPC1) gene. This heterogeneous knockout pool, generated by CRISPR/Cas9-mediated gene disruption, avoids clonal artifacts and better represents the natural genetic diversity of tumor cells. It is designed for rigorous loss-of-function studies of GPC1 in a hepatic cancer context.
SK-HEP-1 cells originate from the ascitic fluid of a male hepatocellular carcinoma patient and exhibit mixed epithelial/mesenchymal features characteristic of aggressive liver cancers. As a neoplastic liver epithelial cell line, it retains key tumorigenic properties, including anchorage-independent growth and in vivo tumor formation. This background enables investigation of GPC1 in the context of hepatocarcinogenesis and cellular plasticity.
GPC1 encodes a heparan sulfate proteoglycan co-receptor that potentiates signaling by heparin-binding growth factors such as FGF2, HGF, and VEGFA. It interacts with receptors FGFR1 and MET to facilitate activation of the RAS-ERK and PI3K-AKT pathways. Downstream effectors include ERK1/2, AKT, CTNNB1, SMAD2/3, and GLI1, while upstream regulators TGFB1, HIF1A, MYC, and ETS1 control GPC1 expression. Knockout of GPC1 abrogates ligand-induced phosphorylation of ERK1/2 and AKT, impairing proliferation, migration, and survival.
In hepatocellular carcinoma, GPC1 is linked to tumor growth, angiogenesis, and metastasis via FGF, HGF/MET, and VEGF signaling. The SK-HEP-1 knockout model allows direct assessment of GPC1’s role in these pathways and in epithelial-mesenchymal transition, which is facilitated by the cell line’s mixed phenotype. This system aids in identifying GPC1-dependent oncogenic mechanisms and therapeutic vulnerabilities.
Applications include studying GPC1 in liver cancer progression, target validation, and drug screening. Representative assays involve Western blotting for phospho-ERK and phospho-AKT, RT-qPCR, cell proliferation (CCK-8/MTT), wound healing/Transwell migration, apoptosis flow cytometry, and xenograft tumor models. For further details or custom inquiries, please contact Ascent Research.