The ACSS2 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of human pancreatic ductal adenocarcinoma cells carrying a disrupted ACSS2 gene. This pool, generated without clonal isolation, represents a heterogeneous knockout model suitable for studying loss-of-function effects in a KRAS/TP53-mutant background.
The parental PaTu 8988t cell line originates from a primary pancreatic cancer and is widely employed as a model for invasive pancreatic ductal adenocarcinoma. These cells harbor oncogenic KRAS and inactivating TP53 mutations, recapitulating key genetic drivers of pancreatic cancer. Their aggressive phenotype and metabolic characteristics make them a relevant platform for investigating tumor metabolism and therapy resistance.
ACSS2 encodes an acetyl-CoA synthetase that ligates acetate with CoA to produce acetyl-CoA, a pivotal metabolite at the intersection of lipid biosynthesis and histone acetylation. ACSS2 is regulated by HIF-1?? and SREBP1 in response to hypoxia and nutrient stress, and its product acetyl-CoA is utilized by fatty acid synthase (FASN) for palmitate synthesis and by histone acetyltransferases to modify chromatin marks such as H3K9ac and H3K27ac. ACSS2 cooperates with ACLY, which generates acetyl-CoA from citrate, and functionally interacts with AMPK, ACACA, and HIF-1?? to integrate metabolic signals.
In PaTu 8988t cells, ACSS2 disruption impairs the ability to use acetate as a carbon source, leading to diminished acetyl-CoA pools. This reduces de novo lipid synthesis and histone acetylation, especially under hypoxic or lipid-depleted conditions that mimic the pancreatic tumor microenvironment. Given the reliance of KRAS-driven pancreatic tumors on lipogenesis and epigenetic regulation, ACSS2 knockout in this model uncovers metabolic dependencies and molecular mechanisms that sustain aggressive tumor phenotypes.
This polyclonal knockout model is applicable to studies of pancreatic cancer metabolism, acetate utilization, the tumor microenvironment, and lipid synthesis. Validated assays include western blotting and RT-qPCR for knockout confirmation, acetyl-CoA quantification, ChIP-qPCR for histone acetylation, lipidomics, and functional tests of proliferation, migration, and hypoxia sensitivity. This model supports drug target validation and exploration of metabolic-epigenetic crosstalk. For further information, please contact Ascent Research.
