The JAG2 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited population of SK-HEP-1 cells with targeted disruption of the JAG2 gene. This polyclonal knockout model enables functional studies of Jagged-2 in a liver adenocarcinoma background while preserving genetic heterogeneity, avoiding artifacts from clonal selection. As a research-grade tool, it provides a cost-effective and flexible platform for pathway analysis and high-content screening applications.
SK-HEP-1 cells are a human hepatic adenocarcinoma line derived from ascitic fluid of a patient with liver cancer. Exhibiting epithelial characteristics, this adherent cell line serves as a reliable model for hepatocellular carcinoma studies, including drug response testing and metastasis research. SK-HEP-1 expresses components of the Notch pathway, including JAG2, making it suitable for interrogating ligand-specific signaling in liver oncogenesis.
JAG2 encodes Jagged-2, a transmembrane Notch ligand that activates NOTCH1-4 receptors on neighboring cells. Upon ligand-receptor interaction, sequential proteolysis by ADAM proteases and gamma-secretase releases the Notch intracellular domain (NICD), which forms a nuclear complex with CSL/RBPJ and MAML coactivators to transcribe targets like HES1, HEY1, MYC, and CCND1. JAG2 expression is modulated by upstream regulators including TGF-beta, NF-kB, and E2F, and its signaling is further controlled by MIB1/MIB2-mediated ubiquitination and endocytosis. This pathway regulates cell fate determination, proliferation, and apoptosis, with aberrant JAG2 activity linked to tumor progression and immune evasion.
In liver cancer, JAG2 is frequently overexpressed and associated with stem cell traits, chemoresistance, and metastatic potential. The polyclonal JAG2 knockout in SK-HEP-1 cells allows researchers to dissect ligand-dependent versus -independent Notch functions while maintaining population-level heterogeneity. This model can be used to evaluate changes in cell proliferation, apoptosis, migration, and sphere formation, and to test therapeutic candidates targeting Notch signaling. Co-culture experiments with wild-type cells can reveal trans-interactions critical for tumor-stromal communication.
Applications include western blotting and RT-qPCR validation of JAG2 and downstream effectors; Notch reporter assays; cell viability and apoptosis profiling following drug treatment; transwell migration/invasion screens; and flow cytometry for surface Notch receptor modulation. Further, RNA-seq transcriptomics can identify JAG2-dependent gene networks, and co-immunoprecipitation can verify disrupted ligand-receptor interactions. For customized protocols or additional information, contact Ascent Research.
