ITGB8 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human hepatocellular carcinoma cell line SK-HEP-1. This product features targeted disruption of the ITGB8 gene encoding integrin beta 8. The polyclonal pool contains a heterogeneous mixture of edited alleles, providing a robust loss-of-function model without clonal selection. These cells are a valuable tool for investigating ITGB8-dependent signaling in a hepatic tumor context.
The parental SK-HEP-1 cell line was established from ascites of a patient with liver adenocarcinoma and uniquely co-expresses epithelial and endothelial markers. This phenotype makes it a relevant model for liver cancer metastasis and angiogenesis and is widely used in hepatocellular carcinoma research. The cell line retains oncogenic pathways and endothelial-like properties, enabling studies of integrin-mediated processes in the tumor microenvironment.
ITGB8 pairs exclusively with ITGAV to form the ??V??8 integrin, which binds the latency-associated peptide (LAP) of TGF-??1 and activates latent TGF-??. Active TGF-?? engages T??RII/T??RI receptors, phosphorylating SMAD2/SMAD3 to induce targets like SERPINE1 and CTGF. ITGB8 also activates focal adhesion kinase (FAK) and PI3K-AKT signaling, integrating adhesion with survival. Upstream, TGF-??, HIF1A, and SMADs regulate ITGB8 expression. Knockout abolishes ??V??8-mediated TGF-?? activation, impairing SMAD phosphorylation, downstream gene expression, and FAK/AKT signaling, thereby disrupting adhesion, migration, and angiogenesis.
Within SK-HEP-1 cells, which co-express epithelial and endothelial markers, ITGB8 knockout offers a unique model to study ??V??8’s contributions to hepatocellular carcinoma progression. The loss of TGF-?? activation and integrin signaling is expected to reduce cell adhesion, migration, and angiogenic capacity??critical processes in metastasis. This polyclonal knockout pool avoids artifacts of clonal selection, better representing the heterogeneity of tumor cell populations, and is valuable for evaluating therapeutic interventions targeting the ITGB8-TGF-?? axis.
These knockout cells are ideally suited for western blotting to monitor SMAD2/3 phosphorylation, RT-qPCR for TGF-??-responsive genes (e.g., SERPINE1, CTGF), and immunofluorescence to visualize integrin distribution. Functional assays include cell adhesion and migration/invasion assays, TGF-?? bioactivity measurements, and in vivo tumor xenograft models. Key applications involve elucidating TGF-?? activation mechanisms, validating ITGB8 as a drug target in hepatocellular carcinoma, and exploring crosstalk between integrin and PI3K-AKT pathways in angiogenesis. For further technical details, please contact Ascent Research.
