The ART1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human clear cell renal cell carcinoma (ccRCC) cell line. This product features targeted disruption of the ART1 gene using CRISPR/Cas9-mediated genome editing, resulting in a loss-of-function model suitable for investigating ADP-ribosylation biology in renal cancer. The polyclonal pool retains genetic heterogeneity typical of a non-clonal knockout population, enabling robust assessment of ART1-dependent phenotypes without the confounding effects of single-cell clonal selection.
The 786-O cell line originates from a primary ccRCC isolated from a 58-year-old male patient and harbors a VHL mutation that leads to constitutive HIF1A stabilization. As a widely used epithelial ccRCC model, it provides a relevant genetic background for examining ART1 function in renal oncogenesis, particularly in the context of VHL-HIF pathway dysregulation.
ART1 encodes a glycosylphosphatidylinositol (GPI)-anchored ADP-ribosyltransferase that transfers ADP-ribose from NAD+ to arginine residues on cell surface proteins, including integrin alpha L (ITGAL) and integrin beta 2 (ITGB2). This activity is regulated upstream by TGF-beta and HIF1A, and ART1 modulates downstream effectors such as focal adhesion kinase (FAK) and paxillin, thereby influencing integrin signaling and focal adhesion dynamics. Through post-translational modification of integrins, ART1 controls cell adhesion, migration, and interactions with the tumor microenvironment.
Disruption of ART1 in 786-O cells abolishes ADP-ribosylation of integrins and other cell surface arginine targets, impairing adhesion signaling and potentially altering metastatic behavior. The loss of ART1-mediated modification disrupts ITGAL/ITGB2-dependent focal adhesion formation and may synergize with VHL-deficient HIF signaling to modulate tumorigenicity. This knockout model therefore offers a unique tool to dissect the interplay between ADP-ribosylation and VHL-HIF pathways in ccRCC, providing insights into how extracellular NAD+ metabolism shapes renal cancer cell biology.
This polyclonal knockout pool is well suited for functional studies, including cell adhesion and migration assays, immunofluorescence analysis of integrin clustering, and ADP-ribosylation activity measurements. It serves as a platform for drug target validation, transcriptome profiling via RNA-seq, and co-culture experiments exploring tumor-immune cell interactions. Typical assays include western blotting for ART1 and downstream targets, flow cytometry for surface integrin levels, and proliferation assessments. For further details or technical inquiries, please contact Ascent Research.
