The DSG2 Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the DSG2 gene. Derived from the NCI-H1299 human lung adenocarcinoma cell line, this product provides a mixed population of gene-edited cells for studying desmosomal adhesion and oncogenic signaling without clonal selection bias. It serves as a versatile tool for investigating loss-of-function phenotypes in a metastatic NSCLC context.
NCI-H1299 is an epithelial cell line established from a lymph node metastasis of a lung adenocarcinoma patient. The cells are p53 null and exhibit hallmarks of advanced non-small cell lung carcinoma, including high metastatic capacity and aberrant growth factor pathway activation. This line is extensively used to model lung cancer progression, EMT, and signaling network rewiring, making it a relevant host for studying the interplay between cell adhesion and tumor malignancy.
DSG2 encodes the desmosomal cadherin desmoglein 2, which mediates calcium-dependent cell?Ccell adhesion and connects intermediate filaments via plakoglobin, plakophilin-2, and desmoplakin. DSG2 also scaffolds EGFR and c-Met, activating PI3K/Akt and Ras/Raf/MEK/ERK pathways. Its expression is upregulated by EGFR ligands, Wnt, and TGF-??, and is transcriptionally regulated by AP-1 and ??-catenin/TCF. Downstream, DSG2 promotes ??-catenin activity, cyclin D1 expression, and MMP secretion, thereby integrating adhesive and mitogenic signals.
In the p53-null NCI-H1299 context, DSG2 ablation disrupts desmosome assembly, potentially compromising epithelial barrier function and facilitating EMT-like phenotypes. This provides a unique system to examine how adhesion defects synergize with oncogenic drivers, particularly in NSCLC. Given the frequent EGFR alterations in lung adenocarcinoma, studying DSG2-EGFR crosstalk in these cells may reveal mechanisms of resistance to EGFR-targeted therapies and identify vulnerabilities in adhesion-impaired tumors.
Typical experimental workflows include western blotting of DSG2 and phospho-proteins, immunofluorescence for desmosome components, Transwell and wound-healing assays, proliferation assays, co-immunoprecipitation of DSG2-EGFR complexes, TEER measurements, and RNA-seq analysis. These polyclonal knockout cells are also suitable for high-throughput drug screening to discover compounds targeting adhesion-deficient cancer cells. For additional technical inquiries or assay customization, please contact Ascent Research.
