The DVL2 Knockout 786-O Polyclonal Cells provide a CRISPR/Cas9-edited polyclonal knockout cell population targeting the DVL2 gene in human renal epithelial adenocarcinoma 786-O cells. This heterogeneous pool of DVL2-disrupted cells avoids clonal selection artifacts, facilitating robust functional analyses. DVL2 encodes a key scaffold protein in Wnt signaling; its ablation in this VHL-mutant carcinoma background enables dissection of oncogenic networks.
The 786-O cell line originates from a primary clear cell renal cell carcinoma and carries a biallelic VHL mutation, resulting in constitutive HIF stabilization and pseudohypoxic signaling. This well-characterized model recapitulates features of renal cancer, including angiogenesis and metabolic reprogramming, and is routinely used for VHL-dependent tumorigenesis studies. The VHL-mutant background makes it an ideal host for examining how DVL2 loss impacts renal carcinoma pathways.
DVL2 acts as a cytoplasmic scaffold transducing signals from Wnt-activated Frizzled receptors. In canonical Wnt signaling, DVL2 cooperates with Axin, GSK3??, and CK1?? to inhibit the ??-catenin destruction complex, stabilizing ??-catenin for TCF/LEF-mediated transcription. Non-canonically, DVL2 activates JNK and Rho GTPases (Rac1) to regulate planar cell polarity and cytoskeletal rearrangements, while also triggering Wnt/calcium signals via NFAT. Upstream regulators include Wnt3a, Wnt5a, CK1, and PAR1; key interacting partners comprise Dapper and CK2, highlighting DVL2??s central role in Wnt signal relay.
In 786-O cells, VHL loss-driven HIF activation coexists with Wnt pathway activity. DVL2 knockout here permits interrogation of crosstalk between hypoxic and Wnt/??-catenin programs, potentially revealing how DVL2 modulates ??-catenin levels, TCF/LEF reporter activity, and non-canonical outputs. This model can elucidate mechanisms of renal tumor progression, invasion, and metastatic spread where Wnt signaling cooperates with HIF.
Applications include western blotting of DVL2 and ??-catenin, TOP/FOP flash luciferase assays, RT-qPCR of Wnt target genes (e.g., MYC, CCND1), co-immunoprecipitation with Axin or GSK3??, and functional migration, invasion, and proliferation assays. The polyclonal knockout pool is also amenable to high-throughput drug screening for Wnt pathway inhibitors in renal cancer. For further inquiries, contact Ascent Research.
