DVL2 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the AGS human gastric epithelial line. This mixed population carries disrupted DVL2 alleles, allowing loss-of-function studies of the Dishevelled-2 scaffold protein. The polyclonal format avoids clonal selection, providing a pooled model for evaluating DVL2??s roles in Wnt signaling without the variability of single-cell clones.
AGS cells, derived from a gastric adenocarcinoma (ATCC CRL-1739), serve as a standard model for gastric cancer research. These adherent epithelial cells retain key oncogenic mutations and signaling features, including Wnt pathway responsiveness, making them suitable for dissecting cancer-related pathways.
DVL2 functions as a central scaffold protein that transmits signals from Wnt/Frizzled/LRP5/6 receptors. Upon ligand binding, DVL2 is recruited to the membrane, where it inhibits the AXIN-APC-GSK3?? destruction complex, leading to ??-catenin stabilization and TCF/LEF-dependent transcription of targets like MYC, CCND1, and AXIN2. Simultaneously, DVL2 activates RhoA/Rac1 and JNK via DAAM1 to control cytoskeletal organization and planar cell polarity. DVL2 interacts with PCP components VANGL1/2 and PRICKLE1/2, and its activity is modulated by CK1 and GSK3?? phosphorylation. Thus, DVL2 coordinates both ??-catenin-dependent transcription and PCP pathways.
In gastric cancer, DVL2 overexpression is linked to aberrant Wnt/??-catenin signaling, promoting proliferation, migration, and drug resistance. The AGS knockout model enables dissection of DVL2-specific functions in an isogenic epithelial context, circumventing confounding effects from other pathway alterations. This tool is valuable for comparing DVL2-dependent and independent mechanisms in gastric tumorigenesis.
Researchers can utilize this polyclonal knockout pool for a variety of assays: Western blotting for DVL2 and ??-catenin, RT-qPCR for Wnt target genes, TOP/FOP reporter assays to gauge transcriptional activity, and functional assays like proliferation, wound healing, and Matrigel invasion. Immunofluorescence reveals ??-catenin localization, and drug screening with Wnt inhibitors can probe chemoresistance. These applications support detailed mechanistic studies and therapeutic target validation in gastric cancer. For additional information, please contact Ascent Research.
