The ABHD17C Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population originating from the SK-HEP-1 human liver adenocarcinoma cell line. This gene-disrupted cell pool provides a physiologically relevant loss-of-function model for investigating protein depalmitoylation and oncogenic RAS signaling, preserving population-level heterogeneity while avoiding clonal selection biases.
The parental SK-HEP-1 cell line was established from the ascites of a liver adenocarcinoma patient and is widely employed as a model for hepatocellular carcinoma (HCC) and endothelial cell biology. Its epithelial morphology and preserved signaling alterations offer a relevant hepatocellular context for dissecting how protein lipidation cycles influence malignant phenotypes, particularly given the established role of RAS-driven pathways in hepatic oncogenesis.
ABHD17C encodes a protein depalmitoylase that catalyzes the removal of palmitate modifications from substrates including NRAS and HRAS, functioning in opposition to ZDHHC-family palmitoyltransferases. Regulated by upstream growth factor signaling and mitogenic stimuli, this depalmitoylation cycle dynamically controls the membrane association and signaling competence of its targets. ABHD17C operates upstream of NRAS within the MAPK/ERK cascade: by reversing palmitoylation, it promotes NRAS redistribution from the plasma membrane to endomembranes, attenuating pathway activity. Consequently, ABHD17C disruption increases NRAS palmitoylation, enforcing plasma membrane localization and constitutive RAF?CMEK?CERK signaling that alters downstream transcriptional programs and cellular behavior.
In the SK-HEP-1 hepatocellular carcinoma setting, ABHD17C knockout establishes a model of aberrant NRAS palmitoylation that drives sustained MAPK signaling, reflecting oncogenic processes relevant to HCC progression. This system permits dissection of how defective depalmitoylation contributes to enhanced proliferation, migration, and survival, and it provides a platform for comparative studies across NRAS-dependent diseases such as melanoma and neurodevelopmental disorders.
The ABHD17C Knockout SK-HEP-1 Polyclonal Cells enable a wide array of investigations, including biochemical detection of palmitoylation dynamics via acyl-RAC and biotin switch assays, imaging of NRAS subcellular distribution by confocal microscopy, and functional phenotyping with MTT/CCK-8, colony formation, and Transwell migration assays. They can also be applied in flow-cytometric cell cycle profiling and RT-qPCR analysis of MAPK target genes. The polyclonal knockout format is well-suited for drug target validation, small-molecule screening focused on the palmitoylation cycle, and post-translational modification research in hepatocellular carcinoma. For additional technical details, please contact Ascent Research.
