The ASGR1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population generated from the 786-O human renal cell adenocarcinoma line. This product disrupts the ASGR1 gene, which encodes the major asialoglycoprotein receptor subunit, using CRISPR/Cas9-mediated genome editing without clonal isolation. The resulting mixed population enables loss-of-function analysis of ASGR1-dependent glycoprotein clearance and endocytic trafficking in a cancer-relevant model.
The parental 786-O cell line is an adherent epithelial model derived from primary clear cell renal cell carcinoma (ccRCC). It harbors a von Hippel-Lindau (VHL) mutation leading to constitutive HIF pathway activation and hypoxia signaling deregulation. With a hyperdiploid karyotype, 786-O cells are widely employed for studying ccRCC metabolism, angiogenesis, and therapeutic responses. The tumorigenic and VHL-null background provides a context to explore receptor-mediated processes in renal cancer.
ASGR1 is a C-type lectin receptor that selectively binds glycoproteins with terminal galactose/N-acetylgalactosamine, such as asialoorosomucoid, and triggers their internalization via clathrin-mediated endocytosis. The receptor interacts with clathrin, the AP-2 adaptor complex, and ??-arrestin to direct endocytic cargo to lysosomes for proteolytic degradation. Transcriptional regulation by HNF4A, HNF1A, C/EBP??, and IL-6 modulates ASGR1 expression, while downstream effectors include lysosomal hydrolases. The pathway also involves ASGR2, clathrin heavy chain, AP2M1, and GALNT14.
In 786-O cells, which lack robust hepatic ASGR1 expression, knockout creates a defined null background for dissecting glycoreceptor-mediated endocytosis independently of liver-specific functions. VHL-deficient renal cancer cells exhibit altered endolysosomal trafficking and metabolic rewiring; thus, ASGR1 loss may impact glycoprotein processing and receptor recycling, with potential crosstalk with hypoxia pathways. This model allows investigation of how tumor cells manage desialylated glycoproteins and whether clearance dysregulation contributes to cancer progression. Additionally, given the association of protective ASGR1 variants with reduced cardiovascular risk, these cells enable off-target effect studies in a non-hepatic context.
These polyclonal knockout cells are suitable for asialoorosomucoid uptake assays to quantify endocytosis, Western blot and immunofluorescence for ASGR1 detection, and RT-qPCR/RNA-seq for transcriptomic profiling. Functional assays such as cell viability and migration can assess knockout phenotypic consequences. The model supports the development of liver-targeted drug delivery systems exploiting the asialoglycoprotein receptor and screening of endocytosis modulators. Researchers may also investigate glycan?Creceptor interactions in cancer microenvironment signaling. For additional information or technical inquiries, please contact Ascent Research.
