The ACSS2 Knockout KYSE-150 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal population of KYSE-150 human esophageal squamous cell carcinoma cells harboring targeted disruption of the ACSS2 gene. This heterogeneous knockout model ablates acetyl-CoA synthetase short-chain family member 2 (ACSS2) function, blocking the conversion of acetate to acetyl-CoA. The polyclonal format preserves the inherent genetic diversity of engineered cells, enabling robust loss-of-function experiments without clonal selection.
KYSE-150 is a well-characterized esophageal squamous cell carcinoma line derived from a poorly differentiated tumor, widely employed as a model for studying esophageal cancer biology. These cells retain key oncogenic properties, including dysregulated metabolic pathways, making them especially relevant for investigating nutrient utilization and anabolic metabolism in cancer. The ACSS2 knockout in this genetic background offers a physiologically pertinent system for examining acetate-dependent processes.
ACSS2 catalyzes the ATP-dependent ligation of acetate and coenzyme A to produce acetyl-CoA, a critical metabolite fueling lipid biosynthesis and histone acetylation in cancer cells under metabolic stress. ACSS2 expression is transcriptionally activated by sterol regulatory element-binding proteins (SREBP1 and SREBP2) and hypoxia-inducible factor 1-alpha (HIF1A), and its activity is modulated by AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). Downstream, ACSS2-derived acetyl-CoA is utilized by fatty acid synthase (FASN) for de novo lipogenesis and by histone acetyltransferases such as EP300 to modify chromatin structure, linking nutrient availability to gene regulation. Additionally, ACSS2 functionally interacts with acetyl-CoA acetyltransferase 1 (ACAT1) and indirectly influences ATP citrate lyase (ACLY) activity, positioning it at the intersection of metabolic and epigenetic signaling networks.
In KYSE-150 esophageal carcinoma cells, ACSS2-dependent acetate assimilation sustains acetyl-CoA pools required for membrane lipid production and histone acetylation, thereby supporting proliferation and survival in nutrient-depleted microenvironments. Disruption of ACSS2 in this polyclonal knockout population impairs acetate incorporation into central carbon metabolism, likely attenuating lipogenesis and epigenetic remodeling. This model therefore enables rigorous dissection of ACSS2-mediated metabolic adaptation and its contribution to esophageal cancer aggressiveness, without confounding clonal effects.
Typical research applications include quantifying acetate uptake and acetyl-CoA levels, monitoring histone acetylation by Western blot, assessing lipid accumulation via BODIPY staining, and evaluating cell proliferation using MTT or colony formation assays. Metabolic flux analyses with Seahorse technology and drug response profiling are also facilitated. This knockout tool is ideal for validating ACSS2 as a therapeutic target in metabolic oncology and for exploring resistance mechanisms to therapies that target lipid metabolism. For additional product details or technical support, please contact Ascent Research.
