The DKK1 Knockout 143B Polyclonal Cells provide a heterogeneous pool of 143B human osteosarcoma cells edited by CRISPR/Cas9 to disrupt the DKK1 gene, generating a loss-of-function model that eliminates endogenous Wnt pathway antagonism. This polyclonal population preserves the parental line??s heterogeneity while enabling systematic study of DKK1-dependent signaling.
Derived from a human osteosarcoma, the 143B cell line is highly tumorigenic and metastatic, widely used to model bone cancer progression and metastasis. Its robust Wnt/??-catenin activity and osteoblastic features make it a physiologically relevant platform for investigating DKK1 function.
DKK1 is a secreted Wnt antagonist that binds LRP5 and LRP6 co-receptors with high affinity, cooperating with Kremen proteins KREMEN1 and KREMEN2 to trigger receptor internalization. This prevents formation of the Wnt?CFZD?CLRP5/6 signaling complex, blocking ??-catenin stabilization and TCF/LEF-dependent transcription. In the knockout cells, loss of DKK1 derepresses the pathway, leading to elevated ??-catenin levels and increased expression of target genes such as MYC, CCND1, AXIN2, and LEF1. DKK1 transcription is itself controlled by upstream regulators including p53 and TGF-??, integrating stress and growth factor signals.
Ablation of DKK1 in 143B cells provides a valuable model for dissecting how Wnt pathway activation influences osteosarcoma cell proliferation, migration, and metastatic dissemination. Because of the line??s intrinsic aggressiveness and ability to spontaneously metastasize, this knockout population is especially useful for preclinical studies of bone cancer biology and for evaluating DKK1-targeted therapies. It additionally offers insights into bone remodeling and diseases where DKK1 is dysregulated, such as osteoporosis and multiple myeloma.
These polyclonal knockout cells are optimized for a variety of experimental approaches, including TOP/FOP luciferase reporter assays to measure ??-catenin transcriptional activity, western blotting for ??-catenin and phospho-LRP6, and RT-qPCR quantification of Wnt target genes. They are well suited for functional assays such as Transwell migration and invasion, cell proliferation analyses, and RNA-seq transcriptomic profiling. Immunofluorescence for ??-catenin localization and inhibitor screening further extend the model??s utility. For additional technical information, please contact Ascent Research.
