The IGSF8 Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the human urothelial carcinoma cell line UM-UC-3. Engineered for loss-of-function studies of IGSF8, this product provides a heterogeneous pool of cells with disrupted IGSF8 alleles, enabling assessment of gene function without clonal selection bias. The polyclonal format reflects the diverse editing outcomes typical of CRISPR/Cas9-mediated gene disruption. Researchers should confirm IGSF8 ablation by appropriate validation assays.
The UM-UC-3 cell line originates from a male patient??s bladder transitional cell carcinoma, serving as a robust model for invasive urothelial cancer. These cells exhibit hallmark features of bladder cancer, including dysregulated EGFR signaling and altered cell adhesion, making them pertinent for studying tumorigenic mechanisms and metastatic progression.
IGSF8 (EWI-2) is a negative regulator of EGFR signaling that promotes receptor degradation and restricts ligand-induced activation. It localizes to tetraspanin-enriched microdomains via interactions with CD81 and CD9, where it modulates integrin-mediated cell adhesion and migration. Specifically, IGSF8 associates with integrin alpha4beta1 and suppresses downstream PI3K/AKT and MAPK/ERK pathways. Consequently, IGSF8 disruption leads to increased EGFR phosphorylation, elevated AKT phosphorylation (Ser473), and enhanced ERK1/2 phosphorylation, activating FAK and SRC. Upstream regulators such as EGF, integrin ligands, and cytokines thus impinge on IGSF8 to control cellular responses. By dampening EGFR and integrin signaling, IGSF8 influences adhesion, migration, and proliferation. This knockout model facilitates dissection of these interconnected pathways.
In UM-UC-3 bladder cancer cells, IGSF8 loss likely exacerbates EGFR-driven oncogenic signaling and integrin-mediated invasive behavior, mirroring observations in urothelial carcinoma and other cancers where IGSF8 expression is often suppressed. This polyclonal knockout population is thus valuable for investigating how IGSF8 depletion affects tumor cell adhesion to extracellular matrix, collective migration, and drug sensitivity. It also provides a platform to study tetraspanin web dynamics and cross-talk between EGFR and integrin signaling axes.
Applications include western blotting for IGSF8, EGFR, p-AKT, and p-ERK; RT-qPCR for transcript analysis; immunofluorescence for tetraspanin localization; and flow cytometry for CD81/IGSF8 surface expression. Functional assays??migration, invasion, proliferation, adhesion??can quantify phenotypic changes. Co-immunoprecipitation with CD81 or CD9 probes protein interactions, while RNA-seq reveals transcriptomic impacts. The model is also suited for drug sensitivity screens. For further inquiries, contact Ascent Research.
