JAG1 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-mediated polyclonal knockout population originating from the AGS human gastric adenocarcinoma cell line, engineered to disrupt the endogenous JAG1 locus. This polyclonal format encompasses a diverse array of edits, providing a genetically varied pool that minimizes clonal selection artifacts and is well-suited for pooled functional genomics and high-throughput screening. The cells serve as a loss-of-function model for investigating Jagged1-dependent signaling and phenotypes.
The AGS cell line is a widely studied model of human gastric adenocarcinoma, derived from a primary gastric tumor and retaining key oncogenic mutations. These adherent epithelial cells exhibit robust growth, predictable transfection efficiency, and compatibility with CRISPR/Cas9 editing, making them a reliable host for genetic modification. Their gastric cancer background offers direct relevance for examining JAG1??s role in tumor biology, including proliferation, invasion, and drug response.
JAG1 encodes Jagged1, a Notch ligand that activates signaling via NOTCH1, NOTCH2, or NOTCH3 receptors. Ligand-receptor interaction triggers ADAM17-mediated shedding and gamma-secretase cleavage, releasing the NICD. NICD complexes with RBPJ and MAML to drive transcription of targets such as HES1, HEY1, MYC, CCND1, and SNAI1, while repressing CDH1. JAG1 expression is upregulated by HIF1A under hypoxia, by TGFB1 and IL-6 stimulation, and by NFKB1, positioning Jagged1 at the nexus of microenvironmental cues that orchestrate cell fate, EMT, and proliferation.
In gastric adenocarcinoma, Jagged1-mediated Notch signaling contributes to tumor aggressiveness by driving epithelial-mesenchymal transition (EMT), maintaining stem cell characteristics, and enhancing metastatic potential. AGS cells with JAG1 disruption provide a clean loss-of-function context to dissect these roles, enabling interrogation of downstream targets like SNAI1 and modulation of cell invasion. This model supports therapeutic target validation and examination of crosstalk with Wnt and hypoxic pathways, all within a clinically relevant gastric cancer genetic background.
This polyclonal knockout population is well-suited for Notch signaling analysis, gastric cancer progression studies, and preclinical drug target validation. Researchers can employ Western blotting to detect JAG1 and NICD, RT-qPCR to quantify HES1 and HEY1 induction, and Notch reporter assays to monitor pathway activity. Co-culture systems enable assessment of ligand-dependent Notch activation. Functional assays including wound-healing and transwell invasion evaluate EMT and metastatic potential, while RNA-seq provides unbiased transcriptomic profiling. For further information or to discuss custom gene-edited cell products, please contact Ascent Research.
