The JAG2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human NCI-H1975 non-small cell lung cancer (NSCLC) cell line, with targeted disruption of the JAG2 gene. This loss-of-function model allows investigation of JAG2-dependent signaling in lung adenocarcinoma. The polyclonal nature provides a heterogeneous knockout pool, avoiding clonal artifacts from single-cell lines.
The NCI-H1975 cell line is a well-characterized model of lung adenocarcinoma, harboring two key epidermal growth factor receptor (EGFR) mutations: L858R in exon 21 and T790M in exon 20. These activating mutations confer sensitivity to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs), while the T790M mutation is associated with acquired resistance to first-generation inhibitors. The cell line is extensively utilized to study EGFR-driven oncogenesis, drug resistance mechanisms, and the tumor microenvironment in NSCLC.
JAG2 encodes Jagged?2, a transmembrane ligand of the Notch receptor family that mediates juxtacrine signaling crucial for cell fate decisions, proliferation, and differentiation. As a component of the Notch signaling pathway, JAG2 interacts with NOTCH1 and NOTCH3, triggering sequential proteolytic cleavages by ADAM17 and the ???secretase complex (presenilin?1, PSEN1). This releases the Notch intracellular domain (NICD), which translocates to the nucleus, associates with the transcription factor RBPJ, and drives expression of target genes including HES1, HEY1, MYC, CCND1, and SNAI1. JAG2 expression is regulated by upstream factors such as MYC, NF???B, HIF?1??, and TGF???, embedding it within networks that control epithelial?mesenchymal transition (EMT) and cancer stem cell maintenance.
In the context of NCI-H1975 cells, JAG2 knockout provides a powerful tool to dissect Notch-dependent contributions to NSCLC pathology. Constitutive Notch activation has been implicated in tumor initiation, maintenance of cancer stem cell populations, and development of resistance to EGFR?targeted therapies. In this polyclonal knockout model, loss of JAG2 function is expected to attenuate Notch signaling, potentially impairing expression of downstream effectors such as HES1 and SNAI1, which are key mediators of EMT and invasion. Consequently, these cells are particularly suited for investigating how JAG2-driven Notch activity interacts with EGFR mutation?driven signaling to modulate cellular plasticity, tumor heterogeneity, and therapeutic response.
Researchers can employ these JAG2 knockout cells in a variety of experimental workflows to elucidate the role of Notch ligand-mediated signaling in lung adenocarcinoma. Common applications include quantitative analysis of Notch pathway component expression by western blotting and RT?qPCR, functional assessment of cell migration and invasion, evaluation of cancer stem cell properties via spheroid formation assays, and profiling of drug sensitivity changes in response to EGFR inhibitors or other therapeutics. The polyclonal knockout format also supports pooled functional genomics approaches and in vitro preclinical testing. For more information, please contact Ascent Research.
