The DOCK11 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt expression of the DOCK11 gene in the 786-O human renal cell carcinoma line. This loss-of-function model comprises a heterogeneous pool of cells carrying various DOCK11 null alleles, enabling robust functional interrogation of DOCK11-dependent pathways without the biases of clonal selection. The polyclonal format preserves cellular diversity while providing a consistent knockout background for diverse experimental applications.
The parental 786-O cell line is a well-characterized model of clear cell renal cell carcinoma (ccRCC), derived from a primary clear cell adenocarcinoma. These epithelial cells are VHL-deficient, lacking functional von Hippel?CLindau tumor suppressor protein, which results in constitutive activation of hypoxia-inducible factors (HIFs) and mimics the hypoxic tumor microenvironment. 786-O cells are tumorigenic in xenograft models and are extensively used for hypoxia-driven signaling, drug resistance, and metastasis research in kidney cancer.
DOCK11 functions as a guanine nucleotide exchange factor (GEF) that specifically activates RAC1 and CDC42 by promoting GDP/GTP exchange. In innate immune signaling, DOCK11 is recruited to the TLR4-MyD88 complex upon LPS stimulation, leading to RAC1-mediated activation of downstream targets such as PAK1 and JNK. This signaling cascade drives actin cytoskeleton reorganization, lamellipodia formation, cell migration, and phagocytosis. DOCK11 also links TLR4 engagement to PI3K-dependent pathways, coordinating cytoskeletal dynamics with innate immune responses.
In the VHL-deficient 786-O background, DOCK11-mediated RAC1 and CDC42 activation may collaborate with hypoxia-driven signaling to enhance the migratory and invasive properties characteristic of ccRCC. The loss of DOCK11 in this context allows researchers to dissect its specific contributions to tumor cell motility, actin remodeling, and TLR4-mediated inflammatory responses, while controlling for the confounding effects of HIF stabilization. This model is thus instrumental for studying the crosstalk between DOCK11-dependent cytoskeletal regulation and hypoxic tumor biology.
These polyclonal knockout cells are ideal for cell migration and invasion assays (wound healing, transwell), phagocytosis assays, and RAC1-GTP pull-down experiments to quantify active RAC1. They support drug sensitivity screening, GEF inhibitor evaluation, and western blotting for phospho-PAK and phospho-JNK. Immunofluorescence detection of F-actin and lamellipodia provides direct visualization of cytoskeletal changes. For further technical details, protocols, and ordering information, please contact Ascent Research.
