The JAG1 Knockout SK-OV-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the human ovarian adenocarcinoma cell line SK-OV-3. This product consists of a heterogeneous pool of cells carrying targeted disruption of the JAG1 gene, which encodes the Notch ligand Jagged1. The polyclonal format offers a robust loss-of-function model for studying JAG1-mediated signaling without clonal artifacts, suitable for a wide range of functional and mechanistic assays.
SK-OV-3 is a well-characterized human ovarian adenocarcinoma cell line established from the ascites of a 64-year-old female. These cells exhibit epithelial morphology and are widely employed as a model for high-grade serous ovarian carcinoma, harboring mutations in TP53 and PIK3CA. Their adherent growth, tumorigenicity, and extensive molecular characterization make them a preferred platform for CRISPR/Cas9-mediated gene disruption in ovarian cancer research.
JAG1 encodes a transmembrane ligand that activates NOTCH1, NOTCH2, and NOTCH3 receptors through direct cell?Ccell contact. Ligand binding triggers sequential cleavage by ADAM10/ADAM17 and gamma-secretase, releasing the Notch intracellular domain (NICD). NICD translocates to the nucleus and complexes with CSL/RBP-J and Mastermind-like (MAML) coactivators to induce target genes such as HES1 and HEY1. JAG1 expression is regulated by upstream factors including TGF-beta, TWIST1, SNAI1, ZEB1, and HIF1A, while downstream effectors encompass MYC, cyclin D1, p21, and mesenchymal markers like Vimentin and N-cadherin, linking JAG1 to epithelial-to-mesenchymal transition (EMT) and proliferation.
In SK-OV-3 cells, JAG1-mediated Notch signaling contributes to cancer stem cell maintenance, EMT, and angiogenesis. Disrupting JAG1 in this polyclonal population allows investigation of Notch pathway addiction and metastatic mechanisms. The heterogeneous knockout pool better reflects intratumoral genetic diversity, enabling studies on drug sensitivity, invasion, and tumor microenvironment interactions.
This knockout model supports diverse experimental applications: Western blot for JAG1 depletion, RT-qPCR for HES1/HEY1, immunofluorescence for NICD localization, and co-culture Notch reporter assays. Functional assays include migration, invasion, and cell viability with gamma-secretase inhibitors, alongside RNA-seq transcriptome profiling. These empower drug target validation, EMT and metastasis research, cancer stem cell biology, and functional genomics. For further information, contact Ascent Research.
