The DOCK2 Knockout SK-HEP-1 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal population derived from the SK-HEP-1 human cell line, featuring targeted disruption of the DOCK2 gene. This polyclonal knockout product provides a heterogeneous loss-of-function model that preserves the genetic background of the parental cells while eliminating DOCK2 protein expression across a pool of edited cells. The use of polyclonal knockout cells is particularly advantageous for studying gene function in a population context, avoiding clonal artifacts and allowing direct comparison with wild-type controls. Researchers can employ this model to investigate DOCK2-dependent processes in liver-derived endothelial-like cells, leveraging the inherent tumorigenic properties and endothelial characteristics of SK-HEP-1. The product is suitable for a range of in vitro assays, including migration, invasion, and signal transduction analyses.
The host SK-HEP-1 cell line is an immortalized human liver adenocarcinoma line originally isolated from the ascitic fluid of a patient with hepatic adenocarcinoma. SK-HEP-1 cells display an endothelial-like morphology and express Factor VIII-related antigen, making them a widely used model for liver sinusoidal endothelial cells (LSECs) as well as for hepatic cancer biology. Their dual nature allows simultaneous investigation of hepatocarcinoma cell behavior and endothelial cell functions. SK-HEP-1 cells are adherent, exhibit robust proliferation, and are amenable to genetic manipulation and downstream functional assays. In the context of liver pathophysiology, they serve as a platform to examine tumor?Cstroma crosstalk, vascular mimicry, and intrahepatic immune cell trafficking, all of which are relevant to hepatocellular carcinoma progression and metastasis.
DOCK2 (Dedicator of Cytokinesis 2) encodes a Rac-specific guanine nucleotide exchange factor (GEF) that is predominantly expressed in hematopoietic cells but also plays roles in certain non-hematopoietic contexts. Mechanistically, DOCK2 is recruited to the plasma membrane and activated downstream of chemokine receptors (e.g., CXCR4, CCR7) via PI3K-generated PIP3. In complex with ELMO1 or ELMO2 and the adaptor CRKII, DOCK2 catalyzes GDP/GTP exchange on Rac GTPases, particularly Rac1 and Rac2. This activation triggers the WAVE complex and Arp2/3-mediated actin polymerization, driving lamellipodia formation, directed cell migration, and T cell activation. DOCK2 thus serves as a critical node connecting chemokine signaling, actin cytoskeletal reorganization, and immune cell function, with additional links to T cell receptor and B cell receptor signaling pathways.
Disrupting DOCK2 in the SK-HEP-1 background enables dissection of its role in liver cancer cell motility and endothelial-like behaviors. Although DOCK2 is best known for its function in immune cells, its expression in SK-HEP-1 and possible involvement in cancer cell migration make this knockout model a valuable tool for liver cancer metastasis research. The endothelial phenotype of SK-HEP-1 further permits exploration of DOCK2’s contribution to processes such as transendothelial migration, vascular network formation, and tumor microenvironment interactions. Given DOCK2’s established links to combined immunodeficiency and immune cell trafficking, this model may also facilitate coculture experiments investigating hepatocarcinoma-immune cell interactions, providing insights into immune surveillance evasion and the tumor microenvironment in hepatic malignancies.
This DOCK2 knockout polyclonal cell population supports a broad spectrum of research applications. It is well suited for chemotaxis assays, Rac activation pull-downs, western blotting, and immunofluorescence-based localization studies to confirm loss of DOCK2 and assess downstream effector signaling. Functional assays such as transwell migration, invasion, and wound healing can quantify the impact of DOCK2 loss on cell motility. Furthermore, the cells can be employed in drug target identification screens aimed at inflammatory and autoimmune disorders, as well as in tumor microenvironment research where DOCK2-dependent actin dynamics affect cellular crosstalk. For further details or to inquire about custom services, please contact Ascent Research.
