The ACSS2 Knockout SK-OV-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the ACSS2 (acyl-CoA synthetase short chain family member 2) gene in human SK-OV-3 ovarian adenocarcinoma epithelial cells. This polyclonal population provides a heterogeneous loss-of-function model for investigating ACSS2-dependent cellular processes. Supplied as a pool of gene-disrupted cells, it enables the study of metabolic and epigenetic functions of ACSS2 in cancer research.
SK-OV-3 cells originate from the ascites of a 64-year-old Caucasian female with high-grade serous ovarian adenocarcinoma. They exhibit a near-triploid karyotype and inherent resistance to cisplatin and other chemotherapeutics. This tumorigenic and metastatic model recapitulates aggressive disease features, including metabolic adaptation and hypoxic responses, providing a relevant background for probing ACSS2 contributions to cancer fitness.
ACSS2 converts acetate to acetyl-CoA, a key substrate for lipid synthesis and histone acetylation. Under hypoxia or nutrient stress, ACSS2 is transcriptionally upregulated by HIF-1??, SREBP-1, and c-Myc. Acetyl-CoA fuels de novo lipogenesis via ACC1 and FASN, leading to lipid droplet formation, and provides acetyl groups for histone H3 acetylation by P300 and CBP, thereby linking metabolism to epigenetic regulation. ACSS2 also engages with AMPK and ACLY at the nexus of energy sensing and biosynthetic pathways.
In SK-OV-3 cells, ACSS2 sustains acetyl-CoA pools during metabolic constraints, potentially promoting epigenetic reprogramming through histone H3 hyperacetylation. This may enhance expression of genes driving proliferation, survival, and drug resistance, contributing to the aggressive, cisplatin-resistant phenotype. Disruption of ACSS2 in this polyclonal knockout population thus allows dissection of acetate metabolism in high-grade serous ovarian cancer pathophysiology, including metastatic and chemoresistant traits.
Applications include cancer metabolism, hypoxia biology, epigenetics, and drug resistance studies. Representative assays: Western blotting for ACSS2 and histone acetylation, RT-qPCR for lipogenic genes, Oil Red O lipid droplet staining, Seahorse metabolic flux analysis, acetate uptake assays, ChIP for H3 acetylation, and cell-based proliferation, migration, invasion, and drug sensitivity tests. For support, contact Ascent Research.
