The DVL3 Knockout AGS Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the human DVL3 gene has been disrupted via targeted genome editing. This product is provided as a population of polyclonal AGS cells carrying heterogeneous CRISPR/Cas9-mediated gene disruptions, offering a versatile loss-of-function model for studying DVL3-dependent biology without clonal selection. It is designed for researchers seeking to interrogate Wnt signaling, gastric cancer progression, or DVL3-associated pathways in a disease-relevant epithelial background.
The host cell line, AGS, is a widely used human gastric adenocarcinoma epithelial cell line originally derived from a 54-year-old female patient. AGS cells exhibit characteristics of primary gastric tumors and are extensively employed in gastrointestinal cancer research, including studies of tumor cell proliferation, migration, drug response, and epithelial-mesenchymal transition (EMT). Their epithelial origin and gastric cancer context make them particularly suitable for modeling Wnt pathway perturbations relevant to gastric malignancy.
DVL3 encodes a cytoplasmic phosphoprotein that functions as a pivotal scaffold in both canonical and non-canonical Wnt signal transduction. Mechanistically, DVL3 is recruited by activated Frizzled receptors and LRP5/6 co-receptors, leading to inhibition of the destruction complex composed of AXIN1, APC, CK1??, and GSK3??. This results in the stabilization and nuclear accumulation of ??-catenin, which partners with TCF/LEF transcription factors to drive expression of target genes such as MYC, CCND1, and AXIN2. Additionally, DVL3 activates non-canonical planar cell polarity (PCP) signaling through RhoA and JNK cascades, regulating cytoskeletal dynamics and cell polarity. DVL3 interacts with a network of proteins including DVL-associated activator of morphogenesis 2 (DAAM2), Dapper, FRAT1, and Naked cuticle homolog 2 (NKD2), and its activity is modulated by upstream kinases CK1?? and GSK3??.
In the AGS gastric cancer model, DVL3 knockout abrogates the canonical Wnt/??-catenin transcriptional program, resulting in diminished expression of proliferation and survival genes such as MYC and CCND1. Loss of DVL3 also disrupts non-canonical signaling, likely attenuating RhoA-mediated migration and invasion essential for gastric cancer metastasis. This disruption renders the DVL3 Knockout AGS Polyclonal Cells a powerful tool to elucidate DVL3??s role in gastric tumorigenesis, EMT, and chemoresistance, and to evaluate efficacy of Wnt-targeted therapeutics in a gastric adenocarcinoma background.
This knockout model is ideally suited for a broad range of experimental applications. Researchers can employ Western blotting and RT-qPCR to validate DVL3 loss and downstream effects on ??-catenin stabilization and target gene expression. Functional assays such as TCF/LEF luciferase reporter systems, CCK-8 proliferation, transwell migration/invasion, and flow cytometry enable quantitative assessment of Wnt-driven phenotypes. Additional applications include ??-catenin immunofluorescence, RNA-seq transcriptome profiling, and co-immunoprecipitation for DVL3 interaction analysis. This knockout population also supports xenograft tumor growth models and high-throughput screening for Wnt pathway inhibitors. For detailed batch-specific information and technical support, contact Ascent Research.
