The DOCK4 Knockout SK-HEP-1 Polyclonal Cells offer a CRISPR/Cas9-edited polyclonal knockout population of the DOCK4 gene in human liver adenocarcinoma SK-HEP-1 cells. This loss-of-function model disrupts the coding sequence of DOCK4, a critical guanine nucleotide exchange factor for Rac1 and Rap1. The polyclonal nature ensures a heterogeneous knockout profile, minimizing clonal selection bias and enhancing experimental robustness for studying DOCK4-dependent pathways in an epithelial cancer context.
SK-HEP-1 is an epithelial cell line isolated from the ascitic fluid of a liver adenocarcinoma patient, routinely employed in hepatocellular carcinoma and metastasis research. These cells possess invasive and migratory capabilities, making them well-suited for dissecting the molecular underpinnings of tumor cell dissemination. The DOCK4 knockout in this background creates a compelling model to examine how disruption of a key GEF impacts the metastatic behavior of liver cancer cells.
DOCK4 operates as a GEF, activating Rac1 and Rap1 by facilitating GDP-to-GTP exchange. It is recruited by ELMO1/2 and is regulated upstream by integrin ??v??3, EGFR, PDGFR, Src, and PI3K. Upon activation, DOCK4 stimulates Rac1 signaling to PAK and the Arp2/3 complex, driving cofilin-mediated actin remodeling. Concurrently, Rap1 activation influences integrin-mediated adhesion. Importantly, DOCK4 couples to ??-catenin stabilization, promoting nuclear translocation and TCF/LEF-dependent transcription. Interactions with Par3 and CrkL further connect DOCK4 to cell polarity and migration pathways, highlighting its central role in integrating adhesion and cytoskeletal dynamics.
In SK-HEP-1 liver cancer cells, DOCK4 loss is anticipated to attenuate Rac1/Rap1 signaling, impair actin reorganization, and reduce ??-catenin transcriptional activity. This directly affects cell migration and invasion, processes pivotal for hepatocellular carcinoma metastasis. The knockout model thus provides a focused system to interrogate DOCK4’s contribution to metastatic progression and to validate therapeutic strategies targeting the DOCK4?CELMO?CRac1/??-catenin axis.
This polyclonal knockout cell population is suitable for an array of applications, including wound healing and transwell invasion assays, Rac1 activation measurements, Western blotting, immunofluorescence, and co-immunoprecipitation. It also enables ??-catenin/TCF reporter gene assays and transcriptomic profiling (RNA-seq) to identify downstream effectors. Applications extend to drug target validation and tumor microenvironment studies. For additional information, contact Ascent Research.
