The CBL Knockout AGS Polyclonal Cells represent a human CRISPR/Cas9-edited polyclonal knockout cell population in which the CBL gene has been disrupted to create a loss-of-function model. This product is provided as a heterogeneous pool of edited AGS cells, each carrying distinct CBL-targeting edits introduced by non-homologous end joining, and is suitable for studies requiring modulation of CBL-dependent regulatory networks. The polyclonal format preserves population-level diversity while eliminating functional CBL expression, enabling robust assessment of CBL-dependent phenotypes in gastric cancer biology without clonal bias.
The host AGS cell line was originally established from a human gastric adenocarcinoma and is characterized by its epithelial morphology and tumorigenic properties. Widely adopted as a model system for gastric cancer, AGS cells exhibit key oncogenic signaling pathways including constitutive activation of receptor tyrosine kinases. This cell line serves as a foundational platform for investigating mechanisms of gastric carcinogenesis, metastatic progression, and therapeutic resistance, making it an ideal background for targeted gene disruption studies.
CBL encodes an E3 ubiquitin-protein ligase that functions as a critical negative regulator of signal transduction. The protein is activated by upstream kinases such as EGFR, PDGFR, and SRC family kinases, and it mediates ubiquitination of activated receptors and downstream effectors including EGFR, PDGFR, SYK, and ZAP70. Through interactions with adaptor proteins like GRB2, CRK, and SLAP, CBL assembles multi-protein complexes that facilitate proteasomal degradation of its targets. Its activity attenuates signaling through the MAPK/ERK and PI3K-AKT pathways, positioning CBL as a principal checkpoint in receptor tyrosine kinase signaling and cellular homeostasis.
In the AGS gastric cancer context, CBL disruption removes a key brake on EGFR-driven proliferative and survival signals. Without functional CBL, activated EGFR is not efficiently cleared, leading to sustained downstream signaling via ERK and AKT cascades. This aberrant signaling is directly relevant to gastric adenocarcinoma pathology, where upregulated EGFR activity promotes cell growth, invasion, and drug tolerance. The CBL knockout AGS model therefore provides a physiologically relevant system to interrogate how loss of this ubiquitin ligase recapitulates aggressive tumor phenotypes and uncovers synthetic lethal vulnerabilities.
This knockout cell population supports a spectrum of experimental applications in gastric cancer research. Investigators can employ Western blotting for CBL, RT-qPCR, and EGFR phosphorylation analysis to verify target disruption and pathway activation. Functional assays such as MTT proliferation tests, Transwell migration/invasion studies, and flow cytometry-based apoptosis assessments quantify phenotypic consequences of CBL loss. Drug sensitivity assays and co-immunoprecipitation studies focusing on the EGFR-CBL interaction further enable exploration of resistance mechanisms and protein complex dynamics. For technical inquiries, please contact Ascent Research.
