The DLG1 Knockout NCI-H1975 Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human NCI-H1975 lung adenocarcinoma epithelial cell line, featuring targeted disruption of the DLG1 gene. This polyclonal pool retains genetic heterogeneity inherent to non-clonal knockout populations, offering a physiologically relevant loss-of-function model that minimizes clonal bias. The product is suitable for functional assays requiring stable DLG1 depletion without the confounding influences of single-cell adaptation.
The parental NCI-H1975 line is a well-characterized human lung adenocarcinoma model harboring the EGFR L858R/T790M double mutation, which drives constitutive EGFR signaling and resistance to first- and second-generation tyrosine kinase inhibitors. This genetic context renders NCI-H1975 cells addicted to mutant EGFR for survival and proliferation, making them an ideal platform for investigating drug resistance and tumor-suppressive pathways in non-small cell lung cancer.
DLG1 encodes a MAGUK scaffold protein at tight junctions and basolateral membranes, coordinating cell polarity and signal transduction. It recruits the tumor suppressors PTEN and APC to the membrane, facilitating ??-catenin degradation and PI3K pathway inhibition. DLG1 is regulated by Aurora A kinase and CDK5 and interfaces with Wnt and Hippo pathways. By scaffolding Scribble complex components (LIN7, CASK, MPP5), DLG1 promotes Hippo kinase (MST1/2, LATS1/2) signaling, restraining YAP/TAZ transcriptional activity. Loss of DLG1 thus relieves YAP/TAZ-mediated transcription and weakens junctional integrity, promoting a pro-invasive state.
In NCI-H1975 cells, DLG1 knockout ablates a key tumor-suppressive hub. By disrupting PTEN and APC membrane localization, the knockout potentiates PI3K/AKT and Wnt/??-catenin signaling, while attenuated Hippo pathway activity unleashes YAP/TAZ-driven transcription. This cooperates with oncogenic EGFR to enhance invasion and may modulate drug sensitivity. The polyclonal nature captures population-level heterogeneity, enabling robust dissection of DLG1-dependent interplay with EGFR signaling.
This product enables diverse applications, including mechanistic studies of cell polarity, Hippo/Wnt pathway crosstalk, and invasion in EGFR-mutant NSCLC. Researchers can utilize western blotting for DLG1, p-YAP/YAP; immunofluorescence for tight junction markers; migration/invasion and proliferation assays; RNA-seq for transcriptomic profiling; and co-immunoprecipitation to examine complex disruption. Drug sensitivity testing with EGFR inhibitors further probes resistance mechanisms. For additional details, please contact Ascent Research.
