The JAG1 Knockout UM-UC-3 Polyclonal Cells constitute a CRISPR/Cas9-mediated gene-disrupted polyclonal cell population within the UM-UC-3 human bladder transitional cell carcinoma background. This loss-of-function model targets the JAG1 locus, enabling investigation of Jagged1-dependent signaling in a defined cancer context. The polyclonal format reflects a heterogeneous pool of edited alleles, providing a robust tool for studying gene function without clonal selection artifacts. The cells are suitable for functional genomics, pathway dissection, and high-content screening applications in cancer biology.
The UM-UC-3 cell line was established from a biopsy of a human male bladder transitional cell carcinoma and harbors a mutant TP53 gene. These cells are tumorigenic in immunodeficient mice and serve as an established model for invasive bladder cancer and metastasis research. The aggressive phenotype of UM-UC-3, combined with defined genetic lesions, offers a relevant system for dissecting molecular drivers of tumor progression, including Notch signaling contributions.
JAG1 encodes Jagged1, a transmembrane ligand for Notch receptors (NOTCH1, NOTCH2, NOTCH3). Upon cell?Ccell contact, Jagged1 engages Notch, triggering sequential proteolysis by ADAM10/17 metalloproteases and the gamma-secretase complex (including PSEN1 and NCSTN), which releases the Notch intracellular domain (NICD). NICD translocates to the nucleus, forms a transcriptional activation complex with RBPJ and MAML1, and drives expression of downstream targets like HES1, HEY1, MYC, CCND1, and AKT. JAG1 expression is regulated by upstream signals such as TGF-beta, HIF-1alpha, EGF, TNF-alpha, ETS1, NF-kB, and the miR-200 family. Additionally, JAG1 can be modulated by interactions with Delta-like ligands DLL1 and DLL4, and its signaling intersects with MAPK/ERK, PI3K/AKT, and Wnt/beta-catenin pathways, placing it at a hub of cellular fate decisions, EMT, and angiogenic control.
In bladder cancer, JAG1-Notch signaling is frequently associated with promotion of epithelial-mesenchymal transition (EMT) and increased invasive capacity. The UM-UC-3 knockout model allows precise dissection of Jagged1’s contribution to these malignant phenotypes, particularly in the context of mutant TP53. By disrupting JAG1 in a tumorigenic background, researchers can delineate its context-dependent roles??whether as a tumor suppressor or oncogenic driver??and explore how cross-talk with other pathways influences motility, survival, and metastatic dissemination.
Applications of these polyclonal JAG1-knockout cells include Notch reporter assays to assess pathway activity, Transwell migration and invasion assays to evaluate EMT functional consequences, immunofluorescence and flow cytometry to quantify receptor expression and signaling complex formation, and RNA-seq or ChIP-qPCR to profile genome-wide transcriptional changes. The system is ideal for drug development screens targeting Notch pathway components, mechanistic studies of bladder cancer metastasis, and tumor microenvironment investigations. For further information, please contact Ascent Research.
