The DVL3 Knockout HeLa Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the HeLa human cervical adenocarcinoma cell line, featuring disruption of the Dishevelled Segment Polarity Protein 3 (DVL3) gene. This heterogeneous loss-of-function model enables robust examination of DVL3-dependent Wnt signaling without clonal selection artifacts. The polyclonal format provides a population-level functional ablation, ideal for characterizing phenotypic consequences of DVL3 deficiency in an epithelial cancer context.
HeLa cells, immortalized from a cervical adenocarcinoma in 1951, are a fundamental epithelial model in biomedical research. Their tumorigenic origin and extensively characterized genome make them well-suited for investigating oncogenic signaling pathways. The epithelial nature supports studies of planar cell polarity and migration, processes where DVL3 exerts regulatory control through both canonical and non-canonical Wnt branches.
DVL3 is a cytoplasmic scaffold that relays signals from Wnt-activated Frizzled receptors. In the canonical Wnt/??-catenin pathway, binding of ligands such as WNT3A promotes DVL3 recruitment and interaction with AXIN1, GSK3??, and CK1, inhibiting the destruction complex (AXIN1, APC, GSK3??, CK1??) and stabilizing ??-catenin (CTNNB1). ??-catenin then partners with TCF/LEF transcription factors like TCF7L2 to induce target genes (AXIN2, MYC). In non-canonical Wnt/PCP signaling, DVL3 activates JNK and c-Jun via DAAM1, RhoA, and RAC1, controlling cytoskeletal dynamics and cell polarity. DVL3 activity is modulated by CK1??, CK2, and DACT1, positioning it as a critical node in Wnt signal diversification.
In HeLa cells, where Wnt signaling is often deregulated, DVL3 knockout offers a pertinent model to dissect its role in tumorigenic phenotypes such as proliferation, migration, and invasion. Disrupting DVL3 is expected to attenuate ??-catenin-driven transcription and impair non-canonical outputs like JNK-mediated cytoskeletal reorganization. The polyclonal pool reduces clonal bias, enabling averaged readouts suitable for drug screening. This model facilitates examination of DVL3 contributions to cervical adenocarcinoma pathobiology and epithelial-to-mesenchymal transition.
Applications include ??-catenin reporter assays (TOPFlash/FOPFlash), immunofluorescence for ??-catenin localization, Western blotting for DVL3 and downstream effectors (phospho-JNK, active ??-catenin), and transwell migration/invasion assays. Co-immunoprecipitation can map DVL3 interaction partners (AXIN1, FZD, DACT1). RNA-seq enables transcriptomic profiling, while pharmacological studies can test Wnt inhibitors. High-content screening for planar cell polarity modulators is also feasible. Contact Ascent Research for further information.
