The CD44 Knockout 786-O Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population of the human 786-O renal cell carcinoma line, engineered to disrupt the CD44 gene. This product provides a heterogeneous pool of cells harboring targeted gene disruptions, enabling loss-of-function studies of the CD44-encoded cell surface adhesion receptor. As a polyclonal knockout model, it reflects the diversity of editing outcomes across the population and is suitable for pooled assays and population-level analyses.
The parental 786-O cell line is derived from a human clear cell renal cell carcinoma (ccRCC) and is deficient in the von Hippel-Lindau (VHL) tumor suppressor, a hallmark of the majority of sporadic ccRCCs. These cells constitutively express hypoxia-inducible factor 1?? (HIF-1??) due to VHL loss, driving a pseudohypoxic transcriptional program. 786-O cells serve as an established in vitro model for studying renal cancer biology, including pathways of tumor growth, metastasis, and drug resistance.
CD44 acts as the primary receptor for hyaluronic acid and co-receptor for osteopontin, mediating cell adhesion and migration. Its cytoplasmic tail binds ERM proteins (ezrin, radixin, moesin), linking to actin and activating RhoA/ROCK-dependent cytoskeletal reorganization. CD44 engagement stimulates the PI3K/AKT/mTOR survival axis and RAS/RAF/MEK/ERK proliferative cascade, while also promoting ??-catenin stabilization and Snail-mediated EMT. In 786-O cells, CD44 is transcriptionally induced by HIF-1??, EGF, and TGF-??. Knockout of CD44 disrupts these interactions, impairing PI3K/AKT and ERK signaling, reducing MMP-9 expression, and attenuating hyaluronic acid?Cinduced migration and actin remodeling, thereby providing a powerful tool to dissect CD44-driven malignant phenotypes.
In the VHL-deficient 786-O renal cell carcinoma model, CD44 knockout is particularly valuable for dissecting pathways of ccRCC metastasis. Constitutive HIF-1?? activation drives CD44 overexpression, linking hypoxic adaptation to enhanced invasiveness. Loss of CD44 compromises adhesion, migration, and EMT, and allows researchers to examine the interplay between hypoxia, hyaluronan signaling, and ERM-mediated cytoskeletal dynamics. This model is thus well-suited to evaluate CD44 as a therapeutic node and to explore mechanisms of resistance in renal cancer.
Typical applications include renal cell carcinoma metastasis research, cell adhesion and migration studies, hyaluronic acid signaling pathway analysis, drug resistance mechanisms, and EMT and cancer stem cell research. Representative experimental techniques compatible with these polyclonal knockout cells include western blotting, RT-qPCR, flow cytometry, immunofluorescence, hyaluronic acid adhesion assays, transwell migration/invasion assays, MTT proliferation assays, apoptosis assays, RNA-seq, and ChIP-qPCR. For detailed protocols, customization options, or ordering information, please contact Ascent Research.
