The DVL2 Knockout HGC-27 Polyclonal Cells product is a heterogeneous population of CRISPR/Cas9-edited HGC-27 gastric adenocarcinoma cells harboring targeted disruption of the DVL2 gene. This polyclonal knockout cell pool provides a physiologically relevant loss-of-function model for interrogating Dishevelled-2 (DVL2)-dependent signaling networks. The polyclonal format maintains population-level heterogeneity, enabling robust functional studies of DVL2 within a mixed genetic background that more closely mirrors cellular diversity encountered in tumor biology.
The parental HGC-27 line is a widely used model of human gastric adenocarcinoma, originally isolated from a lymph node metastasis of an undifferentiated carcinoma. HGC-27 cells retain characteristic features of aggressive gastric cancer, including rapid proliferation, invasive capacity, and aberrant activation of Wnt signaling, making them an ideal host for investigating DVL2 function in metastatic progression.
DVL2 serves as a central cytoplasmic scaffold in the canonical Wnt/??-catenin pathway and the non-canonical planar cell polarity (PCP) pathway. Upon Wnt ligand (e.g., WNT3A, WNT1) engagement with Frizzled receptors and LRP5/6 co-receptors, DVL2 is activated by CK1 and GSK3??-mediated phosphorylation, leading to the recruitment of the AXIN/APC/GSK3?? destruction complex to the plasma membrane. This membrane-proximal complex formation inhibits ??-catenin ubiquitylation and proteasomal degradation, allowing ??-catenin to accumulate, translocate to the nucleus, and associate with TCF/LEF transcription factors to activate target genes such as MYC and CCND1. Additionally, DVL2 independently activates RhoA, Rac1, and JNK signaling branches of the PCP pathway through interactions with DAAM1 and other effectors.
In the context of gastric adenocarcinoma, DVL2 is often overexpressed or hyperactivated, contributing to oncogenic ??-catenin signaling, enhanced proliferation, and metastatic behavior. Disruption of DVL2 in HGC-27 cells abrogates these pro-tumorigenic outputs, providing a powerful tool to dissect the molecular dependencies of Wnt-driven gastric cancer. This model enables identification of critical nodes in the DVL2 interactome, assessment of downstream transcriptional programs, and evaluation of pathway cross-talk with mTOR signaling and other oncogenic networks.
This knockout cell population is suitable for diverse experimental workflows, including quantification of Wnt transcriptional activity via TOP/FOP luciferase reporter assays, analysis of ??-catenin stabilization and subcellular localization by immunofluorescence or Western blotting, and assessment of target gene expression (e.g., MYC, CCND1) by RT-qPCR. Functional assays such as MTT proliferation, transwell migration/invasion, and anchorage-independent growth can be used to delineate DVL2-dependent phenotypes. The polyclonal format also facilitates high-throughput RNA-seq profiling and co-immunoprecipitation studies of the DVL2 protein complex. For additional details, including lot-specific knockout efficiency and recommended culture conditions, please contact Ascent Research.
