The JAG1 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population with targeted disruption of the JAG1 gene. Generated via CRISPR/Cas9-mediated gene knockout, this product abolishes Jagged1 protein expression, creating a loss-of-function model in the NCI-H1703 lung squamous carcinoma background. As a polyclonal pool, it preserves genetic heterogeneity, avoiding clonal artifacts and better representing the diversity of tumor cell populations.
The host cell line, NCI-H1703, originates from a primary lung squamous cell carcinoma of a 54-year-old male smoker. It serves as an established in vitro model for non-small cell lung cancer, particularly the squamous subtype, which is strongly associated with smoking. These cells exhibit adherent growth, rapid proliferation, and invasive properties, making them suitable for studying aggressive tumor behavior.
JAG1 encodes Jagged1, a transmembrane ligand for Notch receptors (NOTCH1, NOTCH2, NOTCH3). Ligand binding triggers cleavage by ADAM10/ADAM17 and ??-secretase (PSEN1), releasing the Notch intracellular domain (NICD). NICD complexes with RBPJ and MAML1 to activate transcription of targets including HES1 and HEY1. Jagged1 expression is driven by upstream regulators such as TGFB1, HIF1A, and NFKB1, and interfaces with WNT and TGF-?? signaling. Downstream, it mediates effects through NOTCH1, MYC, and CCND1 to control cell fate decisions, proliferation, and apoptosis.
In NCI-H1703 lung cancer cells, Jagged1-driven Notch activation contributes to tumor growth and metastatic potential. Knockout of JAG1 disrupts this signaling axis, impairing NICD generation and target gene expression. This model enables dissection of ligand-specific roles in lung squamous carcinoma, including effects on EMT and invasion. It provides a tool to distinguish between the contributions of Jagged1 and other Notch ligands in oncogenic processes.
Applications include detailed characterization of Notch pathway function in lung cancer, assessment of Jagged1 in tumor proliferation and metastasis, validation of therapeutic targets, and screening of Notch inhibitors. Commonly used assays are Western blotting for JAG1 and NICD, RT-qPCR for HES1 and HEY1, luciferase reporter assays, cell viability and apoptosis assays, transwell migration/invasion studies, and xenograft tumor models. For further information, please contact Ascent Research.
