The DOCK5 Knockout 786-O Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal population of human 786-O clear cell renal cell carcinoma (ccRCC) cells, engineered for disruption of the DOCK5 gene. This heterogeneous pool provides a robust loss-of-function model for investigating DOCK5-dependent processes while maintaining population-level genetic diversity and minimizing clonal artifacts.
The parental 786-O line is a VHL-mutant epithelial cell line derived from a primary ccRCC, characterized by constitutive HIF pathway activation and an angiogenic phenotype. This widely used model recapitulates key features of renal carcinoma, including metabolic reprogramming and invasive behavior, making it suitable for dissecting signaling pathways involved in tumor progression.
DOCK5 functions as a guanine nucleotide exchange factor (GEF) for Rac and Cdc42, orchestrating actin cytoskeletal remodeling. Following activation by integrin receptors, EGFR, or PDGFR, DOCK5 forms a complex with ELMO1/ELMO2, which activates Rac1 by promoting GTP exchange. Active Rac1-GTP stimulates downstream effectors such as PAK1 and the WAVE regulatory complex, leading to Arp2/3-dependent actin polymerization, lamellipodia formation, and focal adhesion dynamics. The pathway also integrates Src kinases, PI3K, and adaptors like p130Cas and Crk to modulate cell migration and adhesion.
In VHL-deficient 786-O cells, DOCK5 plays a critical role in promoting the enhanced migratory and invasive capacity characteristic of ccRCC. Disruption of DOCK5 in this model impairs Rac-mediated lamellipodia formation and cell motility, as demonstrated by attenuated migration and invasion upon DOCK5 loss. By linking integrin and growth factor signals to Rac1 activation, DOCK5 contributes to the aggressive behavior of renal carcinoma cells, making these knockout cells a valuable tool for investigating the molecular underpinnings of ccRCC metastasis.
These knockout cells support functional analysis of DOCK5 in migration, invasion, and Rac pathway inhibitor screening. Representative assays include Transwell migration, wound healing, Rac1-GTP pull-down, western blotting for active Rac1, and phalloidin staining for F-actin. The polyclonal format ensures robust population-based assessments, suitable for 3D invasion models and co-culture studies. For additional technical specifications, validation data, or ordering, please contact Ascent Research.
