The IGSF8 Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human hepatic endothelial cell line SK-HEP-1, engineered for loss-of-function studies of the immunoglobulin superfamily member 8 (IGSF8) gene. This gene-edited model is delivered as a heterogeneous pool of cells harboring targeted disruptions in IGSF8, generated without single-cell clonal selection, thereby preserving polyclonal genetic diversity while eliminating functional protein expression. The polyclonal format avoids artifacts associated with clonal expansion and provides a broad representation of the knockout phenotype, making it well-suited for population-level analyses of cell adhesion, migration, and signaling. The product is designed for researchers investigating the molecular determinants of hepatocellular carcinoma progression, tetraspanin web biology, and immune cell recognition events. Each lot is confirmed for IGSF8 protein depletion by Western blot and flow cytometry before shipment.
SK-HEP-1 is a widely used human cell line originally isolated from the ascites fluid of a patient with liver adenocarcinoma, which exhibits an atypical dual phenotype combining both endothelial and epithelial characteristics. These cells express endothelial markers such as von Willebrand factor and CD31, while also displaying features of hepatocarcinoma cells, making them a unique platform to study hepatic sinusoidal endothelium and tumor?Cstroma interactions. SK-HEP-1 has been instrumental in dissecting mechanisms of tumor cell adhesion, transendothelial migration, and angiogenesis. The cell line retains activated signaling pathways common in liver cancer, including elevated PI3K/AKT and ERK1/2 activities, providing a relevant oncogenic background for interrogating metastasis-related gene function. Knockout of IGSF8 in this cellular context allows direct assessment of its tumor-suppressive roles in a model that recapitulates the liver tumor microenvironment.
IGSF8 (also known as EWI-2) functions as a transmembrane cell adhesion molecule of the immunoglobulin superfamily that negatively regulates integrin-mediated cell motility and extracellular matrix attachment through its association with tetraspanin-enriched microdomains (TEMs). Mechanistically, IGSF8 binds directly to tetraspanins CD9 and CD81, as well as to integrin alpha4 (ITGA4) and integrin beta1 (ITGB1), thereby sequestering these partners and suppressing focal adhesion kinase (FAK) phosphorylation and downstream AKT and ERK1/2 signaling. Upstream, IGSF8 expression is modulated by transforming growth factor beta 1 (TGFB1), which represses its transcription, while CD81 stabilizes IGSF8 at the cell surface. In the absence of IGSF8, integrin clustering is enhanced, promoting FAK?CSRC?CPI3K signaling and increased cell migration. Additionally, IGSF8 can modulate natural killer (NK) cell cytotoxicity by altering the lateral mobility of CD81 and other tetraspanins on the plasma membrane, thus linking it to immune surveillance mechanisms.
Disruption of IGSF8 in SK-HEP-1 cells is predicted to relieve its inhibitory constraint on integrin-dependent signaling, thereby enhancing focal adhesion turnover and cell motility. Given the endothelial-like features of SK-HEP-1, this model is particularly relevant for studying the role of IGSF8 in tumor cell adhesion to the hepatic endothelium and extravasation during metastatic dissemination. The knockout is expected to potentiate PI3K/AKT and ERK1/2 cascades downstream of integrin ??1, increasing proliferative and invasive capacity. Because IGSF8 also influences the surface organization of tetraspanin webs that govern cell?Ccell interactions and ligand presentation, its loss may alter immune synapse formation and NK cell?Cmediated cytotoxicity against liver tumor cells. This model thus serves as a valuable tool to dissect the cross-talk between oncogenic signaling and immune recognition in liver cancer.
This IGSF8 knockout polyclonal cell population is ideally suited for a range of advanced research applications, including high-content screening of metastasis inhibitors, detailed mechanistic studies of tetraspanin-mediated signal integration, and evaluation of anti-metastatic drug targets. Typical assays performed with this model include Transwell migration and invasion assays to quantify motility changes, adhesion assays on extracellular matrix components, co-immunoprecipitation of CD81 and ITGB1 to probe tetraspanin complex integrity, and phospho-FAK/AKT analysis by Western blot or flow cytometry to monitor signaling output. The polyclonal nature permits robust statistical comparison to wild-type controls in pooled population formats, minimizing clone-specific effects. Additionally, RNA-seq or qPCR panels can be employed to assess transcriptional alterations in downstream targets such as ERK1/2-responsive genes and integrin-regulatory networks. For further technical details or to request a quote, please contact Ascent Research.
