The INSR Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population designed for loss-of-function studies of the insulin receptor gene. This heterogeneous pool of gene-edited cells enables robust interrogation of INSR-dependent signaling without clonal selection artifacts, while ensuring target-gene disruption across the population.
The parental SK-HEP-1 cell line is derived from the ascites of a liver adenocarcinoma patient and serves as a widely used model for hepatocellular carcinoma research. Its hepatic epithelial origin provides a relevant tumor background for investigating oncogenic and metabolic pathways, making it particularly suited for studying insulin signaling in the context of liver cancer.
INSR encodes the insulin receptor, a receptor tyrosine kinase that, upon insulin binding, autophosphorylates and recruits IRS1 and IRS2. These adaptors trigger the PI3K-AKT pathway, which regulates glucose uptake via GLUT4 translocation and glycogen synthesis via GSK3?? inhibition, and the RAS-MAPK (ERK1/2) cascade, promoting cell proliferation. Upstream regulators include insulin, IGFs, and PTPN1/PTP1B, while downstream targets encompass AKT, mTORC1, FOXO1, and S6K. Interacting factors such as SHC1, GRB2, and PIK3R1 further coordinate this signaling network.
In SK-HEP-1 cells, knockout of INSR abolishes insulin-mediated metabolic and mitogenic signaling, creating a potent model to dissect the insulin receptor??s role in hepatic tumor biology. This system facilitates the study of insulin resistance mechanisms, as SK-HEP-1 cells retain aspects of hepatic metabolic regulation, and allows investigation of the crosstalk between insulin signaling, glucose metabolism, and oncogenic processes in hepatocellular carcinoma and metabolic disorders like non-alcoholic fatty liver disease.
Research applications include insulin sensitizer screening, compound evaluation, and functional metabolic analyses in liver cancer. Typical assays involve Western blotting for phospho-AKT and phospho-ERK, 2-NBDG glucose uptake, glycogen synthesis measurement, MTT cell proliferation, wound healing, and drug sensitivity testing. This polyclonal knockout population is an essential tool for diabetes and metabolic syndrome research. For further information, please contact Ascent Research.
