The DLG1 Knockout NCI-H1299 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population offering constitutive disruption of the DLG1 gene in a non-small cell lung carcinoma (NSCLC) background. Generated by transient CRISPR/Cas9 delivery, this heterogeneous knockout pool avoids clonal selection biases and retains the biological diversity of the parental NCI-H1299 line while abolishing DLG1 expression, making it a versatile tool for functional genomics and signaling network dissection.
The host NCI-H1299 cell line, established from a lymph node metastasis of lung adenocarcinoma, is a widely used p53-deficient NSCLC model. These adherent epithelial cells exhibit aggressive growth characteristics, high metastatic potential, and genomic instability; they are frequently employed in studies of tumor cell motility, invasion, and molecular signaling, providing a disease-relevant platform for evaluating DLG1 function.
DLG1 (SAP97) is a membrane-associated guanylate kinase scaffold that orchestrates the assembly of supramolecular complexes at tight junctions and adherence junctions. It is activated by WNT3A stimulation, E-cadherin (CDH1) engagement, and SRC kinase phosphorylation, and interacts with CASK, LIN7, MPP7, APC, CTNNB1, and PTEN. DLG1 critically regulates Hippo and Wnt pathway dynamics by modulating YAP1/TAZ nuclear localization, LATS1/2 phosphorylation, CTNNB1 transcriptional activity, and CDH1 membrane stabilization. Through anchoring pathway components such as MST1/2, LATS1/2, TCF/LEF transcription factors, and the AXIN?CAPC destruction complex, DLG1 coordinates crosstalk between cell polarity and proliferative signals at intercellular junctions.
In the context of p53-deficient NCI-H1299 cells, disruption of DLG1 impairs tight junction integrity and apical-basal polarity, leading to deregulation of Hippo and Wnt outputs. Loss of the scaffold likely promotes YAP1/TAZ nuclear accumulation and alters CTNNB1 stability, while perturbing KRAS and PTEN localization. This polyclonal knockout model recapitulates junctional scaffolding defects characteristic of aggressive NSCLC, and the combined effects on oncogenic signaling may enhance proliferation, migration, anchorage-independent growth, and metastatic dissemination, offering a powerful system for mechanistic dissection.
Researchers can employ this DLG1 knockout polyclonal population to explore gene function in NSCLC, investigate polarity-driven mechanisms of tumor progression, and dissect crosstalk between Hippo and Wnt pathways. The model is suited for synthetic lethal CRISPR screens, drug target validation, and high-content imaging assays. Standard experimental approaches include western blotting and immunofluorescence for pathway markers (e.g., phospho-YAP1, CTNNB1, CDH1), transwell migration and Matrigel invasion assays, real-time proliferation monitoring, RNA-seq transcriptome profiling, and co-immunoprecipitation to assess protein complexes. For further technical specifications or to place an order, please contact Ascent Research.
