The ACOD1 Knockout HGC-27 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HGC-27 human gastric adenocarcinoma cell line, engineered for targeted disruption of the ACOD1 gene. This polyclonal knockout pool provides a heterogeneous mixture of edited cells with ACOD1 gene disruption, enabling loss-of-function studies without single-cell clonal selection. The product serves as a versatile tool for investigating immunometabolic signaling, inflammasome regulation, and tumor microenvironment interactions in the context of gastric cancer.
The HGC-27 host cell line originates from a lymph node metastasis of an undifferentiated gastric carcinoma, representing an aggressive epithelial cancer model. These cells retain key signaling pathways relevant to gastric cancer biology, including inflammatory and metabolic networks. The ACOD1 knockout model leverages this clinically relevant background to explore how itaconate production and downstream immunomodulatory mechanisms influence gastric cancer cell behavior and interactions with immune components.
ACOD1 encodes aconitate decarboxylase 1, which catalyzes the conversion of cis-aconitate to itaconate, a metabolite with potent anti-inflammatory and antimicrobial properties. Expression of ACOD1 is strongly induced by inflammatory stimuli such as LPS, IFN-??, TNF-??, and IL-1?? through TLR4/NF-??B and STAT1/IRF1 signaling. Once synthesized, itaconate acts on multiple targets: it alkylates KEAP1 to activate the Nrf2 antioxidant pathway, inhibits succinate dehydrogenase (SDH) to reduce mitochondrial reactive oxygen species, and blocks NLRP3 inflammasome assembly by targeting NLRP3 and GAPDH. Additionally, itaconate modulates ATF3 and type I interferon responses. In the ACOD1 knockout background, these regulatory circuits are disrupted, allowing examination of itaconate-dependent and -independent signaling events.
In the HGC-27 gastric cancer context, ACOD1 disruption likely potentiates inflammatory signaling and reshapes metabolic adaptation. Given the emerging role of itaconate in the tumor microenvironment, this knockout model permits dissection of how cancer cell-intrinsic ACOD1 activity affects cytokine production, redox homeostasis, and interactions with infiltrating immune cells. The polyclonal population recapitulates the genetic heterogeneity of CRISPR editing, making it suitable for studying gene function in a cell pool context rather than at the clonal level. Researchers can use this model to explore how ACOD1 influences gastric cancer inflammation, migration, and resistance to immune-mediated killing.
Typical applications include immunometabolism research, macrophage polarization studies, inflammasome regulation assays, and investigation of the gastric cancer microenvironment. The product is compatible with diverse experimental readouts such as western blotting, RT-qPCR, cytokine ELISAs, NF-??B and Nrf2 activity reporters, Seahorse metabolic flux analysis, itaconate quantification by LC-MS, and NLRP3 inflammasome activation assays. Functional studies can incorporate flow cytometry, apoptosis, and migration/invasion assays. For further inquiries, please contact Ascent Research.
