The ACSS2 Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population designed to disrupt the acyl-CoA synthetase short chain family member 2 (ACSS2) gene within the human Ca Ski cervical carcinoma cell line. This product provides a heterogeneous pool of cells carrying targeted genomic modifications in the ACSS2 locus, enabling functional studies of ACSS2-dependent metabolic and epigenetic processes. The polyclonal nature of the knockout population mitigates clonal variation and allows researchers to assess average gene-disruption effects across a diverse genetic background, making it suitable for applications where clonal uniformity is not required.
Ca Ski cells are an epithelial adherent cervical carcinoma line originally isolated from a small intestine metastasis. This HPV-16-positive line exhibits hallmark characteristics of HPV-driven transformation, including E6- and E7-mediated p53 and Rb pathway inactivation, and is widely used as an in vitro model for HPV-associated cervical cancer research, particularly in studies of tumor cell metabolism and drug responsiveness.
ACSS2 encodes an acetyl-CoA synthetase that ligates acetate to CoA, producing acetyl-CoA at the crossroads of lipid synthesis, histone acetylation, and energy metabolism. Its activity is phosphorylated and regulated by AMPK, and its transcription is induced by SREBP1 in response to nutrient availability, while hypoxia and acetate levels further modulate expression. The resulting acetyl-CoA directly fuels de novo lipogenesis through FASN and ACC, and serves as the acetyl donor for histone acetyltransferases, thereby linking metabolic state to chromatin modification. Thus, ACSS2 knockout is anticipated to deplete acetyl-CoA pools, impair lipid biosynthesis, alter histone acetylation marks, and affect downstream AMPK signaling.
In Ca Ski cells, where HPV oncoproteins drive heightened anabolism and epigenetic dysregulation, ACSS2-mediated acetate assimilation is posited to maintain lipogenesis and histone acetylation critical for proliferation. Disruption of ACSS2 in this polyclonal population impedes acetate-to-acetyl-CoA conversion, potentially reducing phospholipid and storage lipid synthesis and limiting acetyl group availability for histones, thereby inducing transcriptional reprogramming. This model permits interrogation of the acetate?CACSS2?Cacetyl-CoA axis in conjunction with AMPK/SREBP1/FASN signaling, elucidating how metabolic enzymes influence tumorigenic properties such as anchorage-independent growth in cervical carcinoma.
This ACSS2 knockout polyclonal cell pool is suitable for metabolic tracing with stable isotopes, lipidomic profiling, and ChIP-qPCR or ChIP-seq to assess histone acetylation changes. Functional studies can include proliferation, colony formation, and drug sensitivity assays to gauge therapeutic vulnerabilities. Combining with AMPK modulators helps dissect regulatory loops within the ACSS2?CSREBP1?CFASN network. Verification of knockout efficiency and downstream effectors is readily performed via western blotting and RT-qPCR. For technical inquiries, please contact Ascent Research.
