The LRP6 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from Raji B lymphocytes. This product provides a heterogeneous pool of cells with disrupted LRP6 gene function, enabling loss-of-function studies without clonal selection bias. The knockout model employs general gene disruption, making it suitable for bulk biochemical and functional assays in the context of malignant B-cell biology. Researchers can utilize this tool to investigate LRP6-dependent signaling pathways and their roles in lymphoma pathogenesis.
The Raji host cell line is an Epstein-Barr virus (EBV)-positive Burkitt lymphoma line established from an 11-year-old male patient. Raji cells are suspension-grown B lymphocytes that serve as a standard model for B-cell malignancies, apoptosis research, and EBV biology. They carry MYC translocations and exhibit deregulated growth, providing a well-characterized background to examine the impact of LRP6 disruption. The EBV latency program in these cells further influences survival and signaling networks, offering a multifaceted platform for studying Wnt pathway contributions to lymphomagenesis.
LRP6 encodes a transmembrane co-receptor essential for canonical Wnt/??-catenin signaling. Ligands Wnt1 and Wnt3a promote LRP6 association with Frizzled receptors and Dishevelled (DVL), triggering phosphorylation by GSK3?? and CK1??. This recruits Axin to the membrane, inhibiting the ??-catenin destruction complex. Stabilized ??-catenin enters the nucleus, binds TCF7/LEF1, and activates MYC, CCND1, AXIN2, and other targets. Extracellular DKK1 and SOST antagonize LRP6, while MESD chaperones its folding. LRP6 also intersects mTORC1 and PI3K/AKT pathways, integrating growth and survival cues.
In Raji cells, LRP6-mediated Wnt signaling may contribute to uncontrolled proliferation and apoptotic evasion. Aberrant Wnt activation is observed in various B-cell lymphomas, often cooperating with MYC overexpression. The LRP6 knockout polyclonal cells allow dissection of LRP6-specific functions in malignant B cells. Given the EBV-positive background, this model also facilitates exploration of virus-host interactions that modulate Wnt signaling. LRP6 has been linked to cancers including colorectal and breast, but its role in Burkitt lymphoma remains underexplored; this tool enables direct mechanistic interrogation.
Typical applications include monitoring canonical Wnt activity via TOP/FOP Flash luciferase reporter assays and RT-qPCR quantification of AXIN2 or CCND1 transcripts. Western blotting can confirm LRP6 knockdown and assess ??-catenin and MYC protein levels. Co-immunoprecipitation studies can evaluate disruption of LRP6-Axin complexes. Flow cytometry enables apoptosis and cell cycle profiling, while MTT viability assays permit screening of Wnt pathway inhibitors or chemotherapeutic synergy. For further information, contact Ascent Research.
