The DVL3 Knockout NCI-H1299 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal population of the human non-small cell lung carcinoma (NSCLC) line NCI-H1299, with targeted disruption of the DVL3 gene. This heterogeneous knockout pool permits functional analyses without the need for single-cell cloning, making it ideal for population-level assays. The cells provide a valuable loss-of-function model for dissecting Wnt pathway contributions to lung cancer biology, supplied as a ready-to-use reagent for downstream experimental applications.
NCI-H1299 is an epithelial cell line originally derived from a metastatic lymph node of lung adenocarcinoma. Widely used as an NSCLC model, it exhibits deregulated proliferation, invasive capacity, and chemoresistance, mirroring clinically aggressive disease. The line lacks functional p53 and carries additional genetic alterations, making it a relevant host for studying oncogenic signaling and drug response. In this context, genetic ablation of DVL3 allows direct examination of its role in maintaining malignant phenotypes.
DVL3 encodes a cytoplasmic scaffold protein that transduces Wnt signals from Frizzled receptors and LRP5/6 co-receptors upon binding of ligands such as Wnt3a and Wnt5a. It forms dynamic complexes with Axin, APC, CK1??, and GSK3?? to inhibit ??-catenin degradation, leading to nuclear accumulation and TCF/LEF-mediated transcription of targets like c-MYC and Cyclin D1. Concurrently, DVL3 engages non-canonical pathways by interacting with DAAM1 and VANGL1/2, activating RhoA, Rac1, and JNK to control cytoskeletal dynamics and migration. Thus, DVL3 operates at a signaling junction that coordinates proliferation and motility.
In the NCI-H1299 background, DVL3 knockout is expected to impair both canonical and non-canonical Wnt signaling, reducing oncogenic outputs such as unchecked proliferation, migration, and invasion. The model therefore enables rigorous dissection of DVL3-specific functions in NSCLC, circumventing off-target effects associated with pharmacological inhibitors. It serves as an isogenic system for mechanistic studies and for screening Wnt pathway modulators.
Typical experimental uses include Western blotting for DVL3, ???catenin, and active ???catenin; RT?qPCR of c?MYC, CCND1, and AXIN2; TOP/FOP flash reporter assays; immunofluorescence for ???catenin localization; and functional assays like MTT/CCK?8 proliferation, transwell migration/invasion, wound healing, and flow cytometric cell cycle/apoptosis analyses. Additional applications encompass RhoA/Rac1 activation pull?downs and drug sensitivity profiling. For technical inquiries or ordering, please contact Ascent Research.
