The DOCK11 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma epithelial line, providing a loss-of-function model for DOCK11. This heterogeneous pool of gene disruptions at the DOCK11 locus enables functional studies of this guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase CDC42. The polyclonal nature avoids clonal selection artifacts, allowing robust investigation of DOCK11-dependent signaling processes. These cells are particularly suited for examining how DOCK11 integrates signals from receptors like EGFR, T-cell receptors, and chemokine receptors to modulate cytoskeletal dynamics and cell behavior in an epithelial context.
The parental AGS cell line, established from a gastric adenocarcinoma of a 54-year-old Caucasian female, is a widely used model for gastric adenocarcinoma. These cells retain signaling networks relevant to tumor progression, making them a mainstay for studying gastric cancer cell migration, invasion, and metastasis. By introducing a DOCK11 knockout into this established background, the cells provide a physiologically relevant system to dissect DOCK11’s contribution to gastric adenocarcinoma pathogenesis. The human epithelial origin ensures findings can be directly extrapolated to mechanisms governing gastric cancer biology.
DOCK11 functions as a dedicated GEF for CDC42, forming a tight complex with the adaptor ELMO1 to catalyze GDP/GTP exchange. Active CDC42 triggers a signaling cascade involving PAK kinases, LIMK, and cofilin, promoting actin filament assembly and filopodia formation. Upstream, activation by EGF through EGFR recruits DOCK11 to the membrane, while downstream effectors include the WASP/WAVE complex driving Arp2/3-mediated actin polymerization. DOCK11 also interacts directly with Rho GTPases, modulating cell polarity and directional migration, processes essential for metastasis.
In the AGS gastric adenocarcinoma context, DOCK11 knockout cells enable dissection of tumor cell migration and invasion mechanisms. Because DOCK11 sits at the intersection of actin remodeling and growth factor signaling, its disruption reveals how gastric cancer cells coordinate motility. This model can investigate DOCK11’s role in peritoneal dissemination or lymph node metastasis, and facilitates interrogation of crosstalk with oncogenic pathways like ??-catenin or NF-??B. Comparing wild-type and knockout populations helps identify therapeutic targets to inhibit gastric cancer progression.
These polyclonal knockout cells are optimized for functional assays. Migration and invasion can be quantified via scratch wound and transwell assays, while actin reorganization is visualized by phalloidin staining and F-actin immunofluorescence. Downstream kinase activation is assessed by Western blotting for phospho-PAK and Rho GTPase pulldowns, and gene expression changes are profiled by RT-qPCR. The cells also suit high-content screening for small molecules targeting the DOCK11?CELMO1 interaction or CDC42 activation. For further information, please contact Ascent Research.
