The JAG1 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human lung adenocarcinoma A-549 cell line, enabling loss-of-function studies of the JAG1 gene. This polyclonal population contains heterogeneous Cas9-mediated disruptions at the JAG1 locus, providing a versatile model that captures population-level phenotypic variability.
A-549 cells were established from a human lung adenocarcinoma and are a standard in vitro model for alveolar epithelial physiology and lung adenocarcinoma research. They harbor oncogenic KRAS mutations and readily undergo epithelial-mesenchymal transition, making them ideal for studying lung cancer progression and therapeutic resistance.
JAG1 encodes the canonical Notch ligand Jagged1, which triggers juxtacrine signaling by binding NOTCH1?C4 receptors. This interaction induces ADAM17- and ??-secretase-mediated cleavage (involving PSEN1) to release the Notch intracellular domain (NICD). NICD translocates to the nucleus and forms a complex with RBPJ (CSL) and MAML1, activating transcription of target genes including HES1, HEY1, c-MYC, CCND1, and SNAI1. JAG1 expression is regulated upstream by TGF-??, HIF-1??, IL-6, and oncogenic KRAS, and cooperates with integrins to influence cell adhesion and migration.
In A-549 cells, JAG1-driven Notch signaling promotes proliferation, survival, and EMT, contributing to aggressive tumor behavior and drug resistance. Disrupting JAG1 in this background enables dissection of its role in tumor?Cstroma crosstalk and maintenance of stem-like properties, with relevance to Alagille syndrome, congenital heart disease, and other cancers.
Applications include mechanistic dissection of Notch signaling via CSL luciferase reporter assays, NICD immunofluorescence, and RT-qPCR for target genes such as HES1 and c-MYC; functional EMT analyses through Transwell migration and invasion assays; proliferation (MTT) and apoptosis (Annexin V) measurements; and high-throughput screening of Notch pathway inhibitors. The polyclonal composition supports studies of signaling heterogeneity and pooled CRISPR screens. For further details, please contact Ascent Research.
