The KSR1 Knockout SK-HEP-1 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population in which the KSR1 gene has been disrupted in the SK-HEP-1 human hepatic sinusoidal endothelial-like cell line. This polyclonal product provides a heterogeneous pool of cells with KSR1 loss-of-function, suitable for investigating the scaffold protein??s role in MAPK/ERK signal transduction. The use of a polyclonal format avoids clonal selection artifacts and allows assessment of gene disruption effects across a diverse genetic background, making it ideal for pooled functional assays.
The host cell line SK-HEP-1 was originally derived from the ascites of a patient with liver adenocarcinoma. Despite its adenocarcinoma origin, these cells exhibit a hepatic sinusoidal endothelial-like phenotype, expressing markers such as factor VIII-related antigen and Weibel?CPalade bodies, and thus serve as a model for liver sinusoidal endothelial cells. SK-HEP-1 cells are widely employed in studies of liver cancer biology, sinusoidal function, filtration, and immune surveillance. Their unique phenotype combines malignant and endothelial characteristics, providing a relevant context for examining signaling pathways that drive hepatocarcinogenesis and tumor?Cmicroenvironment interactions.
KSR1 (Kinase Suppressor of Ras 1) acts as a scaffold protein that coordinates the assembly of RAF, MEK, and ERK kinases to transduce signals from activated RAS to ERK. Following growth factor receptor (EGFR, PDGFR) stimulation, KSR1 translocates to the plasma membrane and interacts with RAF1, MEK1/2, and ERK1/2. Scaffold activity is regulated by phosphorylation: CK2 phosphorylation promotes 14-3-3 binding and cytoplasmic retention, whereas PP2A-mediated dephosphorylation enables membrane recruitment and RAF activation. Downstream, ERK phosphorylates transcription factors such as ELK1, leading to c-FOS and MYC expression, thus controlling proliferation and survival.
In SK-HEP-1 cells, which retain aberrant growth factor signaling common in hepatocellular carcinoma, KSR1 disruption provides a tool for dissecting scaffold-dependent ERK activation. Since these cells exhibit active MAPK signaling, the knockout population allows researchers to examine how loss of KSR1 impacts ERK signaling amplitude and downstream transcriptional responses. This model is relevant for studying RAS-driven liver cancers and evaluating whether targeting KSR1 impairs tumor cell proliferation and invasiveness.
Research applications include oncogenic RAS signaling studies, MAPK pathway dynamics, and drug resistance mechanisms. Typical assays are western blotting for KSR1 and phospho-ERK, RT-qPCR for c-FOS and MYC, cell proliferation, migration, and invasion assays, and soft agar colony formation. RNA-seq can further elucidate transcriptome-wide changes. For additional product details and ordering, contact Ascent Research.
