The DTNA Knockout NCI-H1299 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1299 human lung adenocarcinoma epithelial cell line. This product provides a heterogeneous pool of cells harboring targeted disruptions in the DTNA gene, which encodes alpha-dystrobrevin, a critical component of the dystrophin-associated protein complex (DAPC). Without clonal selection, the polyclonal format preserves genetic diversity and functional heterogeneity, enabling robust loss-of-function studies in a physiologically relevant cancer background. The CRISPR-edited polyclonal pool serves as a versatile model to dissect alpha-dystrobrevin-dependent processes in non-small cell lung carcinoma (NSCLC) without the limitations of monoclonal artifacts.
The host cell line, NCI-H1299, was originally isolated from a lymph node metastasis of a 43-year-old Caucasian male with lung adenocarcinoma. As a widely utilized model in cancer research, these cells exhibit characteristics of metastatic NSCLC, including altered adhesion, migration, and survival signaling. The NCI-H1299 line is well-characterized for its genetic background, which includes homozygous partial deletion of the TP53 gene, and its capacity to form tumors in immunocompromised mice. This metastatic context provides a clinically relevant system to explore how DTNA loss influences tumor progression and cellular interactions with the extracellular matrix.
Alpha-dystrobrevin, encoded by DTNA, functions as a structural and signaling scaffold within the dystrophin-glycoprotein complex (DGC), linking the actin cytoskeleton to the extracellular matrix. It directly interacts with dystrophin, syntrophin alpha1, sarcoglycan gamma, and dystroglycan, and its activity is regulated by upstream factors such as serum response factor, MEF2 transcription factors, and mechanical stress. Downstream, DTNA modulates signaling cascades including PI3K-Akt and MAPK pathways, impacting cell adhesion, survival, and migration. Dysregulation of DTNA has been implicated in left ventricular noncompaction, dilated cardiomyopathy, and muscular dystrophy, highlighting its importance in maintaining membrane stability and mechanotransduction.
In the NCI-H1299 background, knockout of DTNA likely disrupts the integrity of the DGC, leading to altered cell?Cmatrix adhesion and enhanced metastatic potential. The loss of alpha-dystrobrevin may impair the docking of signaling molecules such as PI3K and GRB2, thereby attenuating Akt and ERK phosphorylation in response to integrin-mediated adhesion. This perturbation provides a powerful platform to investigate how cytoskeletal-matrix signaling contributes to NSCLC progression, including anchorage-independent growth, invasion, and resistance to anoikis. By dissecting DTNA??s role, researchers can delineate whether it acts as a tumor suppressor or modifier in lung adenocarcinoma.
Researchers can employ these polyclonal knockout cells in a variety of functional assays to examine DTNA??s role in cancer biology. Western blotting and immunofluorescence can assess expression and localization of DAPC components, while co-immunoprecipitation verifies protein?Cprotein interactions. Functional studies may include cell adhesion and migration assays, wound healing, and phospho-signaling analysis for Akt and ERK pathways. These cells are suitable for exploring the dystrophin-glycoprotein complex in NSCLC, evaluating cytoskeletal-matrix interactions in metastasis, and screening for DTNA-interacting partners. For additional technical specifications or custom applications, please contact Ascent Research.
