The DTNA Knockout AGS Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population targeting the DTNA gene in the AGS gastric epithelial cell line. This loss-of-function model is generated through CRISPR/Cas9-mediated gene disruption, resulting in a heterogeneous pool of cells carrying diverse DTNA-inactivating mutations. The polyclonal format ensures representation of multiple knockout variants, making it suitable for studies in which clonal uniformity is not required and population-level functional effects are of primary interest. These cells serve as a versatile tool for dissecting DTNA-dependent processes in a human gastric adenocarcinoma background.
The host cell line, AGS, is a widely used human gastric adenocarcinoma epithelial cell line derived from a patient with gastric cancer. AGS cells exhibit hallmarks of transformed epithelial cells, including dysregulated adhesion and sustained proliferative signaling. Their gastric epithelial origin makes them relevant for investigating molecular mechanisms underlying gastric carcinogenesis and for testing therapeutic interventions targeting gastric tumors. The AGS background provides a physiologically relevant context for studying DTNA function in the gastric mucosa and its potential role in gastric cancer progression.
DTNA encodes dystrobrevin alpha, a scaffold protein that is a critical component of the dystrophin-associated glycoprotein complex (DAPC). Within this complex, dystrobrevin alpha interacts directly with dystrophin, syntrophins, and dystroglycan, as well as with sarcoglycans and utrophin, to anchor the actin cytoskeleton to the extracellular matrix. This linkage is essential for maintaining sarcolemmal integrity in muscle and analogously for preserving membrane stability in non-muscle cells. Upstream of DTNA, mechanosensitive pathways and YAP/TAZ signaling converge to modulate DAPC assembly, whereas downstream, DTNA knockout disrupts RhoA/ROCK, FAK, and MAPK signaling cascades, leading to reorganization of the actin cytoskeleton. Additionally, dystrobrevin-mediated scaffolding facilitates focal adhesion dynamics and integrin-mediated adhesion, underscoring its pleiotropic roles in cellular mechanics and signaling.
In the context of AGS gastric epithelial cells, DTNA loss phenocopies aspects of dystroglycanopathy-related signaling defects, where compromised DAPC function impairs cell adhesion, migration, and proliferation. Given that gastric adenocarcinomas often exhibit aberrant cell-ECM interactions and cytoskeletal reorganization, this knockout model enables investigation of how dystrobrevin alpha deficiency modulates oncogenic pathways in gastric epithelial cells. It also provides a platform to study the crosstalk between mechanical cues and growth factor signaling through DAPC in a cancer-relevant setting. The polyclonal knockout population is particularly valuable for capturing heterogeneous responses that recapitulate the genetic diversity observed in tumor cell populations.
Researchers can employ these DTNA Knockout AGS Polyclonal Cells in a wide range of functional assays. Standard applications include western blotting and immunofluorescence to confirm loss of dystrobrevin alpha protein and assess DAPC complex integrity. Cell adhesion and migration assays enable quantitative analysis of substrate attachment and motility, while proliferation assays reveal growth phenotypes. Co-immunoprecipitation experiments can probe altered protein?Cprotein interactions within the DAPC, and phospho-protein analysis of FAK and Akt provides direct readouts of downstream signaling pathway activity. This product is thus suited for drug screening efforts targeting dystroglycanopathies and for mechanistic studies of cytoskeletal signaling in gastric cancer. For additional technical details, please contact Ascent Research.
