The IL6ST Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt expression of the IL6ST gene, encoding the gp130 signal transducer. This loss-of-function model is derived from the SK-HEP-1 human hepatic adenocarcinoma cell line and provides a genetically controlled system for studying IL-6 family cytokine receptor signaling. The polyclonal nature of the edited cells reflects a mixed population carrying various Cas9-induced modifications at the IL6ST locus, enabling robust functional interrogation of gp130-dependent pathways.
The SK-HEP-1 cell line was originally established from the liver adenocarcinoma ascites of a 52-year-old male and displays an adherent epithelial morphology with both epithelial and endothelial characteristics, mimicking liver sinusoidal endothelial cells. This unique dual phenotype makes SK-HEP-1 particularly relevant for investigating hepatocellular carcinoma biology, tumor microenvironment interactions, and endothelial functions. The cells are widely used for studying liver cancer cell signaling, invasion, and drug responses.
IL6ST (gp130) serves as the shared signal-transducing subunit for the IL-6 cytokine receptor family, including receptors for IL-6, IL-11, LIF, OSM, CNTF, CT-1, CLC, and NP. Upon ligand binding, gp130 dimerizes with a specific ??-receptor chain and activates associated JAK kinases (JAK1, JAK2, TYK2), which phosphorylate downstream transcription factors STAT3 and STAT1, promoting their nuclear translocation and target gene expression. Additionally, gp130 stimulation engages the MAPK/ERK pathway via SHP2?CGRB2?CGab1 complexes and the PI3K/AKT pathway, collectively regulating cell survival, proliferation, and inflammation. Key downstream effectors include SOCS3, BCL2, MYC, VEGF, MMP2, MMP9, Cyclin D1, and HIF1A.
In the SK-HEP-1 hepatic adenocarcinoma background, IL6ST knockout abrogates the cellular response to IL-6 family cytokines, providing a critical model to dissect gp130??s role in liver cancer progression and endothelial-like functions. Given that hyperactive IL-6/STAT3 signaling is implicated in hepatocellular carcinoma growth and metastasis, this knockout cell population allows for precise assessment of gp130 dependency in proliferation, migration, invasion, and cytokine production. It also enables the study of crosstalk between JAK/STAT, MAPK, and PI3K/AKT pathways in a context retaining both epithelial and endothelial traits.
These polyclonal knockout cells are suitable for a range of experimental applications, including IL-6 stimulation assays, STAT3 phosphorylation analysis by western blot, STAT3 luciferase reporter assays, and RT-qPCR quantification of SOCS3 expression. The model supports cell proliferation, migration, and invasion assays to evaluate gp130-mediated tumorigenic behaviors. Additionally, it serves as a platform for drug screening with JAK/STAT inhibitors and for investigating cytokine release syndrome or inflammatory mechanisms in liver-derived cells. For further technical details regarding batch performance and validation data, contact Ascent Research.
