The MET Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte cell line, engineered for loss-of-function studies of the MET gene. This product consists of a heterogeneous pool of cells carrying targeted disruptions of the MET locus, providing a versatile model for investigating MET-dependent signaling without the confounding influence of wild-type protein expression. The polyclonal format captures the genetic diversity inherent to the knockout approach, allowing robust functional analysis in a population context.
The parental Raji cell line originates from an EBV-positive Burkitt lymphoma and harbors the characteristic t(8;14) translocation that juxtaposes the MYC oncogene to the immunoglobulin heavy chain (IGH) enhancer, driving aberrant MYC expression. Raji cells are a well-established model for B-cell malignancies, exhibiting high proliferative capacity and retaining key B-cell receptor signaling pathways. This genetic background makes the MET knockout derivatives particularly relevant for dissecting the interplay between MET signaling and MYC-driven lymphomagenesis.
MET encodes the receptor tyrosine kinase for hepatocyte growth factor (HGF). Ligand binding induces dimerization, autophosphorylation, and recruitment of multisubstrate docking proteins such as GAB1 and GRB2, which interact with SHC, PLC??, and the p85 regulatory subunit of PI3K. This triggers a cascade through the RAS-MAPK pathway (involving SOS, RAS, RAF, MEK, and ERK) and the PI3K?CAKT?CmTOR axis, while also activating STAT3 and promoting ??-catenin stabilization. Upstream regulators include hypoxia, IL-6, and integrins ??6??4 and CD44, which enhance MET signaling. Downstream transcription factors MYC and JUN, along with MMPs, orchestrate proliferative and invasive responses.
In the Raji Burkitt lymphoma background, characterized by t(8;14) MYC/IGH translocation and EBV positivity, MET contributes to the malignant phenotype by transducing microenvironment-derived HGF signals. Disrupting MET expression in this polyclonal population abrogates HGF-induced phosphorylation of AKT and ERK, impairing cell survival and motility. This knockout model permits the uncoupling of MET-driven signals from the dominant MYC oncogenic program, offering a precise tool to assess MET??s role in lymphoma progression and to test targeted therapeutic interventions.
Researchers can confirm MET depletion by Western blot or RT-qPCR and measure signaling attenuation via phospho-AKT/ERK after HGF stimulation. Functional assays include MTS proliferation, Annexin V apoptosis, and Boyden chamber migration/invasion. Typical applications encompass pathway dissection in B cells, MET inhibitor validation, and crosstalk with MYC-driven growth. For further technical details or ordering information, please contact Ascent Research.
