The ACSS2 Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population featuring targeted disruption of the ACSS2 gene in the UM-UC-3 human urothelial carcinoma cell line. This polyclonal model provides a heterogeneous loss-of-function system representative of cancer cell diversity, avoiding the pitfalls of clonal selection. Supplied as a ready-to-use knockout product, it is optimized for advanced research in cancer metabolism and epigenetic regulation.
The parental UM-UC-3 cell line was derived from a male patient with high-grade invasive transitional cell carcinoma of the bladder. The line harbors a TP53 missense mutation (R280T) and an aneuploid karyotype, hallmarks of genomic instability in aggressive bladder cancer. UM-UC-3 is a standard model for studying invasive bladder tumor biology, including metastasis, drug resistance, and metabolic adaptation.
ACSS2 encodes acetyl-CoA synthetase short-chain family member 2, which catalyzes the ATP-dependent ligation of acetate and coenzyme A to form acetyl-CoA. Under nutrient-limited or hypoxic conditions, ACSS2 acts as a principal source of acetyl-CoA for histone acetylation and lipid biosynthesis. ACSS2 expression is transcriptionally regulated by HIF1A, SREBF1, SREBF2, and AMPK in response to metabolic stress. The enzyme replenishes the acetyl-CoA pool that is utilized by acetyltransferases such as EP300 and KAT2A to deposit H3K9ac and H3K27ac marks, modulating chromatin and gene expression. Acetyl-CoA also serves as a substrate for lipogenic pathways, driving expression of FASN and SCD1. ACSS2 interacts with SIRT1 and EP300, key nodes in the metabolic?Cepigenetic crosstalk. The broader pathway involves acetate uptake via MCT1, ACSS2-mediated activation, and downstream partitioning between histone acetylation and lipid synthesis, with ACLY and HDACs influencing overall dynamics.
In UM-UC-3 bladder cancer cells, ACSS2 knockout disrupts acetate-dependent acetyl-CoA production, leading to diminished histone acetylation and suppressed lipogenic gene programs. The TP53-mutated, aneuploid background makes this model especially suited for interrogating the intersection of acetate metabolism, p53 dysfunction, and genomic instability. Under hypoxia or nutrient stress, ACSS2-deficient UM-UC-3 cells are anticipated to show impaired proliferation and reduced tumorigenic capacity, highlighting ACSS2 as a metabolic vulnerability in aggressive urothelial carcinoma.
This polyclonal knockout cell product is ideal for dissecting ACSS2 function in bladder cancer metabolism, investigating nutrient-driven epigenetic regulation, and validating ACSS2 as a therapeutic target. Typical experiments include acetyl-CoA quantification, histone modification profiling (e.g., H3K9ac, H3K27ac), isotopic tracing of acetate into lipids, proliferation assays under hypoxia, soft agar colony formation, and xenograft tumor growth studies. For additional information, please contact Ascent Research.
