The ACOD1 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the PaTu 8988t human pancreatic ductal adenocarcinoma epithelial cell line, featuring targeted disruption of the ACOD1 gene. This loss-of-function model enables investigation of aconitate decarboxylase 1 function and itaconate biology without predefined clonal selection, providing a heterogeneous population that reflects diverse editing outcomes.
PaTu 8988t was established from a liver metastasis of a human pancreatic adenocarcinoma and serves as a well-characterized model for studying tumor invasion, metastasis, and therapy resistance. The epithelial origin and metastatic background make this cell line particularly valuable for investigating molecular mechanisms underlying aggressive pancreatic cancer behavior and metabolic adaptations in secondary tumor sites.
ACOD1 encodes aconitate decarboxylase 1 (also known as IRG1), which catalyzes the decarboxylation of cis-aconitate to itaconate in the TCA cycle. Itaconate acts as a signaling metabolite that inhibits succinate dehydrogenase (SDH), reducing mitochondrial reactive oxygen species and pro-inflammatory cytokine production. Itaconate also alkylates KEAP1, leading to Nrf2 activation and induction of antioxidant response genes, while upregulating ATF3 and I??B?? to limit NF-??B-driven inflammation. ACOD1 expression is robustly induced by pro-inflammatory stimuli such as LPS (via TLR4/MyD88), TNF-??, and IFN-??, mediated by transcription factors NF-??B, STAT1, and IRF1.
In the PaTu 8988t context, ACOD1 knockout allows dissection of tumor-intrinsic itaconate synthesis and its impact on metabolic reprogramming, redox homeostasis, and inflammatory signaling within pancreatic cancer cells. This model is particularly relevant for exploring how itaconate modulates tumor immune evasion and therapy resistance in a metastatic pancreatic cancer background, potentially revealing vulnerabilities in the TCA cycle-inflammatory axis.
Researchers can employ these polyclonal knockout cells for assays including Western blotting for ACOD1, LC-MS-based intracellular itaconate quantification, Seahorse metabolic flux analysis, NF-??B luciferase reporter assays, and transwell invasion assays to assess tumor cell behavior. Applications span studies on metabolic crosstalk in the tumor microenvironment, itaconate-mediated anti-inflammatory mechanisms, and drug screening for modulators of the itaconate pathway. For further details, please contact Ascent Research.
