The DMD Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the NCI-H1975 human lung adenocarcinoma epithelial cell line. This product features targeted disruption of the DMD gene (encoding dystrophin) via CRISPR/Cas9-mediated gene editing, producing a diverse pool of loss-of-function cells. The polyclonal format avoids clonal selection artifacts and provides a heterogeneous model suitable for population-level functional studies. This ready-to-use tool enables investigation of dystrophin biology in a cancer cell context.
NCI-H1975 is a human lung adenocarcinoma cell line derived from a female non-smoker, carrying oncogenic EGFR L858R and tumor suppressor TP53 R273H mutations. As an epithelial cancer model, it is extensively used to study lung tumorigenesis, drug resistance, and signal transduction. Incorporating the DMD knockout into this background allows dissection of dystrophin functions in a malignant epithelial environment, beyond its canonical role in muscle.
Dystrophin is a large cytoskeletal protein linking actin filaments to the extracellular matrix through the dystrophin-glycoprotein complex (DGC). It interacts with actin, ??-dystroglycan, ??-sarcoglycan, syntrophin, dystrobrevin, and nNOS. Transcription is regulated by MyoD, myogenin, MEF2, and SP1. Downstream, the DGC modulates nNOS, MAPK, and AKT pathways. DMD knockout disrupts the DGC, impairing cytoskeleton-ECM linkage and membrane integrity, altering adhesion and signaling.
In NCI-H1975 cells, DMD knockout provides a model to explore dystrophin’s role in cancer cell adhesion, migration, and mechanosensing. Loss of dystrophin may alter responses to mechanical stress and influence invasive behavior, while potential crosstalk with EGFR and TP53-driven pathways through MAPK/AKT cascades offers avenues for studying drug sensitivity and metastasis. This model is particularly relevant for investigation of non-muscle dystrophin functions in solid tumor biology.
Applications include migration/invasion and adhesion assays to assess cell motility and attachment, mechanosensing studies under varied stiffness, and drug resistance profiling against targeted therapies or chemotherapeutics. Expression analysis by RT-qPCR or RNA-seq and protein detection via Western blot and immunofluorescence enable comprehensive characterization. For additional technical details or inquiries, please contact Ascent Research.
