The KCNK3 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human cell line. This product provides a robust loss-of-function model for studying the TASK-1 potassium channel (encoded by KCNK3) in hepatic adenocarcinoma biology. The polyclonal knockout format enables investigation of gene disruption effects without requiring clonal isolation, ensuring a representative and heterogeneous cell pool for reliable phenotypic analysis in downstream applications.
The host cell line, SK-HEP-1, was established from ascites of a patient with liver adenocarcinoma and serves as a widely used model for hepatocellular carcinoma research. These cells exhibit relevant hepatic tumor characteristics, including endothelial-like properties and tumorigenic capacity, and are amenable to a broad range of molecular and cellular techniques. Their well-documented signaling profiles and suitability for transfection and drug treatment make them an ideal platform for studying KCNK3 function in liver cancer and hypoxia-related signaling.
KCNK3 encodes TASK-1, a pH-sensitive two-pore domain K+ channel that maintains resting membrane potential and is regulated by hypoxia, intracellular acidification, serotonin, endothelin-1, PKA, and PKC. TASK-1 interacts with 14-3-3 proteins, SUMO, and syntaxin-1A. In this knockout model, disruption of KCNK3 eliminates TASK-1 K+ currents, causing membrane depolarization and increased calcium influx through L-type Ca2+ channels. This triggers activation of calcineurin, which dephosphorylates NFAT, and concurrent phosphorylation of ERK1/2, driving cell proliferation and survival. Downstream targets include Bcl-2 family proteins, linking TASK-1 to apoptosis regulation.
In SK-HEP-1 cells, KCNK3 knockout disrupts normal hypoxia sensing, mimicking chronic inhibition of TASK-1 and leading to constitutive activation of HIF-1???CTASK-1?Ccalcineurin/NFAT and ERK pathways. This polyclonal knockout population thus provides a valuable tool for dissecting hypoxia-driven oncogenic mechanisms in hepatic adenocarcinoma, including the role of TASK-1 in promoting tumor cell proliferation, migration, and resistance to apoptosis. The model is particularly suited for investigating interplay between ion channel function and liver cancer progression.
Typical applications include pulmonary hypertension modeling, cancer cell signaling studies, hypoxia response analysis, ion channel drug screening, and apoptosis mechanism research. Compatible assays range from patch-clamp electrophysiology and Fluo-4 calcium imaging to western blotting, MTT viability assays, Annexin V apoptosis detection, Transwell migration, and RNA-seq transcriptomics. For further details or technical assistance, please contact Ascent Research.
