The DTNA Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the NCI-H1975 human lung adenocarcinoma cell line. In this product, the DTNA gene has been disrupted via CRISPR/Cas9-based genome engineering, generating a heterogeneous pool of knockout cells. As a population, it serves as a robust model for studying dystrobrevin alpha loss-of-function without the biases of clonal selection.
The NCI-H1975 cell line originates from pleural effusion of a female patient with lung adenocarcinoma and harbors EGFR L858R and TP53 mutations. This widely used EGFR-mutant non-small cell lung cancer model recapitulates oncogenic signaling and acquired resistance to EGFR inhibitors such as osimertinib, making it an ideal platform to study dystrophin-associated complex biology in a kinase-driven setting.
DTNA encodes dystrobrevin alpha, a scaffolding component of the dystrophin-associated glycoprotein complex (DAPC). It binds dystrophin (DMD) or utrophin (UTRN) and the transmembrane dystroglycan (DAG1), while its syntrophin-binding domain anchors SNTA1, SNTB1, and SNTB2. These scaffolds facilitate syntrophin-mediated activation of PI3K/AKT and MAPK signaling, connecting extracellular matrix adhesion to cell survival and proliferation. DTNA is transcriptionally regulated by MEF2 factors and mechanical stress, and it contributes to actin filament stabilization. Thus, DTNA disruption is expected to impair cell-matrix adhesion, mechanotransduction, and downstream kinase cascades.
In NCI-H1975 cells, DTNA knockout provides a model to dissect DAPC involvement in EGFR-driven NSCLC. Loss of dystrobrevin alpha may alter syntrophin-dependent PI3K/AKT and MAPK signaling, potentially modulating EGFR inhibitor sensitivity and migration. The EGFR L858R and TP53 mutations create a clinically relevant context for studying crosstalk between adhesion signaling and oncogenic kinases, and for exploring cytoskeleton-mediated drug resistance mechanisms.
Researchers can utilize this knockout population for a range of functional assays, including western blotting for DAPC components (dystroglycan, syntrophins), immunofluorescence staining for focal adhesion proteins, transwell migration assays, phospho-AKT/phospho-ERK ELISA, and cell adhesion measurements. EGFR inhibitor dose?Cresponse studies with osimertinib allow investigation of drug sensitivity shifts. The polyclonal format enables robust population-level analyses without clonal selection artifacts. For additional information or custom inquiries, please contact Ascent Research.
