The DMD Knockout SK-HEP-1 Polyclonal Cells are a polyclonal cell population derived from the SK-HEP-1 hepatic adenocarcinoma line, in which the dystrophin (DMD) gene has been disrupted via CRISPR/Cas9-mediated gene editing. This knockout model eliminates full-length dystrophin protein, providing a loss-of-function tool for studying dystrophin-dependent cellular processes in a liver tumor context.
The SK-HEP-1 cell line, isolated from the ascites fluid of a patient with hepatic adenocarcinoma, displays a hybrid phenotype combining epithelial and endothelial characteristics. This unique background enables studies of cytoskeletal dynamics, cell-matrix adhesion, and metastatic mechanisms in hepatocellular carcinoma. The cells are anchorage-dependent and compatible with standard culture, transfection, and drug treatment protocols, making them suitable for functional genomics and pharmacological investigations.
Dystrophin is a large cytoskeletal scaffold that bridges the intracellular actin network with the extracellular matrix through the dystrophin-glycoprotein complex (DGC), which includes dystroglycan (DAG1), the sarcoglycan subcomplex (SGCB, SGCG, SGCD), syntrophin (SNTA1), and dystrobrevin (DTNA). In non-muscle cells, dystrophin organizes focal adhesions and modulates signaling by regulating focal adhesion kinase (FAK) autophosphorylation and Src family kinase activity, leading to downstream ERK1/2 and Akt pathway activation. DMD transcription is controlled by upstream factors including MyoD, MEF2C, SP1, and the mechanosensor YAP1, while mechanical stress further regulates its expression. Loss of dystrophin disrupts the DGC assembly, reduces FAK and Src signaling, and attenuates ??-catenin transcriptional responses, collectively impairing cell adhesion and mechanotransduction.
Knocking out DMD in the SK-HEP-1 hepatic adenocarcinoma line creates a relevant model to examine how dystrophin-mediated mechanosignaling influences liver tumor cell behavior. The disruption of actin-matrix linkage is predicted to alter focal adhesion dynamics, cell spreading, and migration, which are key processes in cancer invasion and metastasis. Given the endothelial-like traits of SK-HEP-1, this system also permits analysis of dystrophin??s role in vascular mimicry and tumor microenvironment interactions. The knockout cells thus serve as a platform to identify dystrophin-dependent vulnerabilities in hepatic cancer and to dissect molecular pathways that are otherwise concealed in wild-type cells.
These polyclonal knockout cells are suited for assays such as western blotting and immunofluorescence to verify dystrophin depletion and DGC component redistribution, cell adhesion and wound healing assays to quantify migration impairment, and phospho-FAK/phospho-ERK1/2 analysis to map signaling alterations. RNA-seq transcriptomic profiling can uncover dystrophin-regulated gene networks, while drug sensitivity testing may reveal synthetic lethal interactions for therapeutic targeting. The model is also valuable for evaluating exon-skipping therapies in a non-muscle cancer cell system. For additional information or technical support, please contact Ascent Research.
