The JAG1 Knockout LoVo Polyclonal Cells product is a heterogeneous pool of LoVo cells with CRISPR/Cas9-mediated disruption of JAG1, a key Notch ligand. Derived from the human colorectal adenocarcinoma LoVo line, this polyclonal knockout model enables study of JAG1 functional loss in a cancer-relevant context, averaging clonal variation for pathway-level analysis in tumor biology and signal transduction.
The parental LoVo cell line originates from a metastatic colorectal adenocarcinoma isolated from a male patient. As an epithelial cell model, LoVo recapitulates key features of colorectal cancer progression, including invasive growth patterns and active Wnt and TGF-?? signaling. The metastatic origin of these cells renders them particularly valuable for dissecting molecular mechanisms of tumor dissemination and for evaluating therapeutic targets in advanced disease stages.
JAG1 encodes a transmembrane ligand for NOTCH1-4 receptors, initiating signaling through ADAM protease-mediated shedding and ??-secretase cleavage. The liberated NOTCH intracellular domain partners with the CSL transcription factor and MAML coactivator to promote expression of HES1 and HEY1. JAG1-driven Notch activity is regulated by upstream factors NF-??B, HIF1A, VEGF, and TGF-??, and it controls downstream targets including MYC, SNAI1, SNAI2, and VEGFA, while repressing CDH1. CRISPR/Cas9-mediated gene disruption therefore eliminates ligand-receptor engagement, diminishing HES/HEY transcriptional output and uncoupling Notch-dependent crosstalk with Wnt and TGF-?? signaling networks.
In the LoVo colorectal adenocarcinoma background, JAG1 loss-of-function models the disruption of Notch pathway activity that is frequently dysregulated in colorectal cancer and Alagille syndrome. By preventing ligand-driven Notch activation, these knockout cells permit dissection of JAG1??s role in proliferation, epithelial-mesenchymal transition, and angiogenic signaling. The model is particularly relevant for studying how JAG1 influences the balance between stem-like and differentiated states and for examining compensatory crosstalk between Notch, Wnt, and TGF-?? cascades in a metastatic colorectal cancer context.
This product supports advanced applications in signal transduction, cancer biology, and drug target validation. Typical workflows include Western blotting for JAG1 and NOTCH1, RT-qPCR for HES1/HEY1, flow cytometry for Notch activation, wound healing and transwell migration assays, proliferation curves, and qPCR panels for EMT markers SNAI1 and CDH1. For technical support, contact Ascent Research.
