The IGF1R Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the gene encoding insulin-like growth factor 1 receptor (IGF1R) has been disrupted. This product is supplied as a mixed population of edited cells derived from the SK-HEP-1 human hepatocellular carcinoma cell line, providing a polyclonal loss-of-function model for studies of IGF1R-dependent signaling and cellular behavior.
SK-HEP-1 is a widely used human hepatocellular carcinoma line originally isolated from the ascites of a patient with liver adenocarcinoma. Notably, these cells co-express epithelial and endothelial markers, including cytokeratins and von Willebrand factor, making them a unique model for liver sinusoidal endothelium and a valuable system for studying tumor?Cendothelial interactions in the hepatic microenvironment. Their cancerous origin and dual phenotype allow researchers to investigate both hepatocarcinogenesis and endothelial biology.
IGF1R encodes a receptor tyrosine kinase that is activated by its cognate ligands IGF1 and IGF2, and to a lesser extent by insulin. Ligand engagement triggers receptor autophosphorylation and recruitment of adaptor proteins such as IRS1 and SHC, which serve as platforms for downstream signal propagation. The IRS1?CPI3K?CAKT pathway leads to phosphorylation of key downstream targets including mTOR, FOXO transcription factors, BAD, and GSK3??, collectively promoting cell survival, growth, and metabolism. In parallel, the SHC?CGRB2?CSOS?CRAS?CRAF?CMEK?CERK1/2 cascade drives mitogenic responses. Negative regulation of these pathways is exerted by PTEN, which hydrolyzes phosphatidylinositol (3,4,5)-trisphosphate to counteract PI3K signaling.
Disruption of IGF1R in SK-HEP-1 cells abrogates ligand-induced activation of both the PI3K?CAKT and MAPK?CERK modules, leading to impaired cell proliferation, survival, and metabolic programming. In the context of this hepatocellular carcinoma line, loss of IGF1R function can attenuate anchorage-independent growth, reduce migratory and invasive capacity, and sensitize cells to apoptotic stimuli. Furthermore, because SK-HEP-1 cells retain endothelial-like properties, this knockout model permits investigation of how IGF1R contributes to vascular mimicry and tumor?Cendothelial cell crosstalk. The polyclonal nature of the population captures the heterogeneity of editing events, providing a robust system for studying gene function without clonal bias.
These polyclonal IGF1R knockout cells are suitable for a wide range of experimental applications, including signaling pathway analysis by Western blotting for phosphorylated AKT (Ser473) and ERK1/2 (Thr202/Tyr204), RT-qPCR quantification of downstream transcriptional targets, and phenotypic assays such as MTT and BrdU proliferation measurements, Annexin V apoptosis detection, and Transwell migration/invasion studies. They also serve as an isogenic negative control for evaluating the specificity and efficacy of IGF1R-targeted therapies, including the small-molecule inhibitor linsitinib, in drug sensitivity and resistance experiments. For further inquiries or to acquire this product, please contact Ascent Research.
