The ACSS2 Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the human ACSS2 gene has been disrupted in the SK-HEP-1 hepatic adenocarcinoma cell line. This polyclonal knockout model provides a heterogeneous pool of cells carrying targeted gene disruptions, enabling loss-of-function studies of ACSS2 without clonal selection artifacts. The product is designed for researchers investigating acetate metabolism and its role in cancer cell proliferation, histone acetylation, and metabolic stress responses.
The host cell line, SK-HEP-1, is a widely used human hepatocellular carcinoma model originally derived from the ascites of a patient with liver adenocarcinoma. These cells exhibit epithelial morphology and possess tumorigenic and metastatic properties, including endothelial-like features that facilitate studies of tumor angiogenesis and invasion. SK-HEP-1 cells are commonly employed in hepatocellular carcinoma research due to their well-characterized genetic background and robust growth in culture, making them a suitable platform for investigating oncogenic metabolic rewiring.
ACSS2 (acyl-CoA synthetase short-chain family member 2) catalyzes the conversion of acetate to acetyl-CoA, a critical substrate for de novo lipid synthesis through acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN), as well as for histone acetylation mediated by histone acetyltransferases (HATs). ACSS2 expression is transcriptionally regulated by sterol regulatory element-binding protein 2 (SREBP-2) and hypoxia-inducible factor 1-alpha (HIF-1??), and its activity is modulated by AMP-activated protein kinase (AMPK)-dependent phosphorylation. Downstream, acetyl-CoA generated by ACSS2 feeds into the tricarboxylic acid (TCA) cycle and sustains histone acetylation marks that promote the expression of cell proliferation genes. ACSS2 functionally interacts with HAT complexes and nuclear translocation factors, and co-regulates metabolic gene programs with HIF-1?? under hypoxic conditions.
In hepatocellular carcinoma, ACSS2 is often upregulated in response to hypoxia via HIF-1??, enabling tumor cells to utilize acetate as a nutrient source when glucose is limiting. This metabolic adaptation fuels lipid biosynthesis and maintains histone acetylation landscapes that support oncogenic transcription. The SK-HEP-1 polyclonal ACSS2 knockout model therefore allows dissection of how acetate-derived acetyl-CoA contributes to hepatocellular carcinoma cell proliferation, survival, and epigenetic regulation. By disrupting ACSS2 in a cell line with endothelial-like characteristics, researchers can also explore its role in tumor microenvironment interactions and metastatic potential.
This knockout product is suitable for a broad range of applications, including metabolic flux analysis using Seahorse analyzers, proliferation and migration assays (MTT, Transwell), RNA-seq transcriptomics, ChIP-seq for histone acetylation profiling, and targeted metabolomics of acetyl-CoA and downstream lipids. It is a valuable tool for validating ACSS2 as a therapeutic target in hepatocellular carcinoma and other cancers such as breast, glioblastoma, and prostate cancer. Investigators can employ western blotting, RT-qPCR, and flow cytometry to confirm ACSS2 disruption and assess downstream pathway alterations. For additional technical information, please contact Ascent Research.
