The ACSS2 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the NCI-H1703 human lung squamous cell carcinoma line. This product disrupts the ACSS2 gene, eliminating acetyl-CoA synthetase short-chain family member 2 function across the pool. Researchers can thus study acetate-dependent acetyl-CoA production in a defined genetic background. The polyclonal format maintains population heterogeneity, offering a robust loss-of-function model for pooled screening and bulk biochemical assays, avoiding clonal selection biases.
The parental NCI-H1703 cell line originates from a primary lung squamous cell carcinoma, serving as a widely used non-small cell lung cancer (NSCLC) model. These adherent epithelial cells retain tumor-specific features, including oncogenic signaling and metabolic adaptations. As a squamous NSCLC line, NCI-H1703 is suitable for dissecting metabolic vulnerabilities. Its genetic and phenotypic stability supports reproducible experiments, and its epithelial nature facilitates carcinoma cell biology studies.
ACSS2 catalyzes the ATP-dependent ligation of acetate to CoA to produce acetyl-CoA, a key metabolite for lipid synthesis and histone acetylation. This reaction is critical under nutrient-limited or hypoxic conditions. Upstream regulators SREBP1, AMPK, and hypoxia modulate ACSS2 expression. The acetyl-CoA serves as substrate for FASN and ACC in de novo lipogenesis, and for histone acetyltransferases depositing H3K9ac and H3K27ac. Through these mechanisms, ACSS2 couples acetate availability to anabolic metabolism and epigenetic reprogramming, promoting MYC target gene expression and cell proliferation. ACSS2 interacts with AMPK, ACLY, and importin-??, integrating metabolic and signaling pathways.
In the NCI-H1703 NSCLC context, ACSS2 knockout provides a powerful model to dissect acetate utilization in tumor growth. Lung squamous cell carcinomas frequently encounter nutrient deprivation and hypoxia; acetate recapture from the microenvironment may support survival. Disruption of ACSS2 in this background can uncover dependencies on acetate for lipid biomass accumulation and histone modification-driven transcriptional programs. Consequently, these cells are instrumental for testing therapeutic strategies that target acetate metabolism, as well as for exploring resistance mechanisms to conventional therapies that rely on alternative metabolic substrates.
These polyclonal knockout cells are suitable for a comprehensive array of functional assays. Western blotting confirms ACSS2 protein loss, while RT-qPCR and RNA-seq enable transcriptome-wide analysis. 13C-acetate tracing quantifies acetyl-CoA incorporation into lipids and histones, and ChIP-qPCR maps histone acetylation marks such as H3K9ac and H3K27ac at specific loci. Proliferation assays and drug sensitivity testing assess growth dependencies and compound responses, and flow cytometry can monitor cell cycle progression or apoptosis induction. For further details or to inquire about this product, please contact Ascent Research.
