This product is a CRISPR/Cas9-edited polyclonal knockout cell population targeting the DOCK11 gene in the human SK-HEP-1 cell line. The polyclonal format provides a heterogeneous pool of gene-disrupted cells, enabling robust loss-of-function studies without the need for clonal isolation. By abolishing DOCK11 expression, this model allows researchers to interrogate the role of DOCK11-dependent signaling in hepatocellular carcinoma biology.
The SK-HEP-1 host cell line is a well-characterized human liver adenocarcinoma cell line originally derived from ascitic fluid of a patient with liver adenocarcinoma. Notably, SK-HEP-1 cells display both epithelial and endothelial characteristics, making them a unique model for studying tumor cell plasticity, transendothelial migration, and metastatic dissemination. The dual phenotype also supports investigations into vascular mimicry and the tumor microenvironment.
DOCK11 functions as a specific guanine nucleotide exchange factor (GEF) for the small GTPase Cdc42, catalyzing the exchange of GDP for GTP to generate active Cdc42-GTP. Activation is triggered by upstream chemokine signaling through CXCR4, which stimulates PI3K to produce PIP3. PIP3 directly binds DOCK11, recruiting it to the plasma membrane where it activates Cdc42. Active Cdc42-GTP then engages downstream effectors including PAK1, WASP, and the Arp2/3 complex, ultimately driving actin polymerization and filopodia formation. This signaling axis??CXCR4 ?? PI3K ?? PIP3 ?? DOCK11 ?? Cdc42-GTP ?? PAK1 ?? LIMK ?? cofilin??promotes actin cytoskeletal reorganization and enhances cell motility.
In the context of hepatocellular carcinoma, DOCK11-mediated Cdc42 activation is implicated in tumor cell migration, invasion, and metastasis. The SK-HEP-1 polyclonal DOCK11 knockout model provides a valuable tool to dissect the contribution of this pathway to liver cancer aggressiveness. By eliminating DOCK11, researchers can assess changes in actin dynamics, cell polarity, and invasive capacity, offering insights into potential therapeutic vulnerabilities. Additionally, given DOCK11??s emerging role in immune cell function and inflammation, this model may also facilitate studies intersecting cancer and immunity.
Typical applications include western blotting and RT-qPCR for confirmation of DOCK11 knockout, Transwell migration and invasion assays to evaluate metastatic potential, Cdc42 activation assays to measure GTP-bound Cdc42 levels, phalloidin staining to visualize F-actin organization, cell proliferation assays, and transcriptomic profiling via RNA-seq. These approaches enable comprehensive phenotypic characterization and mechanistic dissection of DOCK11-dependent signaling in liver cancer. For additional information or technical support, please contact Ascent Research.
