The KLRB1 Knockout LoVo Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal population of LoVo human cells with targeted disruption of the KLRB1 gene. This heterogeneous pool reflects diverse knockout events that collectively eliminate CD161 expression, without single-cell cloning. The polyclonal format avoids clonal artifacts and is suited for population-level loss-of-function studies, providing a robust model to investigate the CD161 inhibitory receptor in a colorectal adenocarcinoma background.
The parental LoVo cell line originates from a metastatic colorectal adenocarcinoma of a male patient with Dukes’ type C disease. It exhibits epithelial morphology, microsatellite stability, and known driver mutations KRAS G13D and PIK3CA E545K. These genetic features make LoVo a relevant platform for studying signaling interplay and immune receptor function in colorectal cancer. This knockout derivative enables dissection of KLRB1-specific roles in a molecularly defined tumor context.
KLRB1 encodes CD161, an inhibitory C-type lectin receptor that binds LLT1 (CLEC2D) and recruits phosphatases SHP-1 (PTPN6) and SHP-2 (PTPN11) via ITIM motifs. This recruitment suppresses NFAT and NF-??B signaling, reducing IFN-?? and TNF production. CD161 is transcriptionally regulated by IL-15, IL-12, ROR??t, and STAT3, and its inhibitory output is mediated by SHP-dependent dephosphorylation events that curtail T cell and NK cell effector functions. In LoVo epithelial cells, CD161 signaling may intersect with tumor-intrinsic pathways.
In colorectal cancer, the CD161/LLT1 axis is implicated in immune evasion, as tumor-expressed LLT1 can inhibit anti-tumor lymphocytes. KLRB1 knockout in LoVo cells provides a tractable model for dissecting CD161-mediated inhibitory signaling within tumor cells, independent of immune interactions. This model is particularly relevant given the PIK3CA and KRAS mutations, enabling studies of crosstalk between oncogenic pathways and CD161-controlled signaling circuits.
Researchers can apply this knockout model in assays such as cell proliferation (MTT), wound healing migration, transwell invasion, and colony formation to assess CD161 loss-of-function. Molecular analyses like RT-qPCR and Western blotting confirm KLRB1 disruption, while flow cytometry verifies absence of surface CD161. Phospho-protein profiling of AKT and ERK can reveal pathway alterations, and tumor xenograft studies extend findings in vivo. The cells are also suited for screening immunomodulatory compounds targeting the CD161/LLT1 checkpoint. For technical inquiries and ordering information, please contact Ascent Research.
