The APP Knockout Ca Ski Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Ca Ski human cervical squamous cell carcinoma line. This product provides a heterogeneous pool of edited cells with targeted disruption of the APP gene, enabling loss-of-function studies in an endogenous genomic context. The polyclonal format preserves the natural genetic diversity of the edited population, facilitating robust assessment of APP-dependent phenotypes without clonal selection bias.
Ca Ski cells are an established in vitro model originating from a mesenteric metastasis of a cervical squamous cell carcinoma. They harbor integrated HPV16 DNA and retain key hallmarks of cervical cancer biology, including dysregulated proliferation and metastatic potential. Their epithelial morphology and well-characterized growth characteristics make them a valuable platform for examining oncogenic mechanisms and therapeutic responses, particularly in the context of gene editing approaches.
The amyloid precursor protein (APP) is a type I transmembrane protein that undergoes sequential proteolysis by ??- or ??-secretase (ADAM10 or BACE1) followed by ??-secretase (PSEN1, PSENEN, NCSTN, APH1) to release extracellular fragments and the APP intracellular domain (AICD). AICD translocates to the nucleus and forms a transcriptional regulatory complex with Fe65 and Tip60, modulating expression of genes such as neprilysin, GSK-3??, p53, and EGFR. Beyond its role in amyloid-?? generation, APP participates in cell adhesion and migration via interactions with integrin ??1, LRP1, and Dab1, and integrates signals from the Reelin, Notch, and Wnt pathways. Upstream regulators include BACE1, PSEN1, ADAM17, FE65, NF-??B, and HSF1, positioning APP at a nexus of neurodegenerative and oncogenic signaling.
In the Ca Ski background, APP knockout disrupts AICD-dependent transcriptional programs and cell adhesion dynamics, potentially impairing tumor cell migration and proliferation. The HPV16-positive, metastatic origin of Ca Ski cells provides a relevant context for dissecting APP??s non-amyloidogenic functions in cancer progression. Loss of APP may alter integrin-mediated adhesion and downstream MAPK/PI3K-AKT signaling, thereby affecting cellular responses to the tumor microenvironment. This model thus allows investigation of APP??s dual roles in neurodegeneration and cancer.
Researchers can employ these APP knockout polyclonal cells in a wide array of applications, including amyloid-?? (A??40/A??42) ELISA, western blotting for APP processing intermediates (C99, C83, AICD), and RT-qPCR for AICD target genes. Co-immunoprecipitation assays enable study of APP interactions with BACE1, FE65, or integrins, while secretase activity assays and wound healing migration assays provide functional readouts. The model is also suitable for secretase inhibitor screening, RNA-seq transcriptomic profiling, and cell viability (MTT) or flow cytometric analyses. For further information, please contact Ascent Research.
