KYNU Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human A-549 lung adenocarcinoma cell line, designed for loss-of-function studies of the KYNU gene. This product comprises a heterogeneous mixture of cells with targeted gene disruption of the kynureninase gene, enabling investigation of KYNU-dependent processes without the need for clonal isolation. The polyclonal format maintains genetic diversity within the population, reducing clonal bias in experimental readouts. These cells serve as a powerful tool for probing the role of kynureninase in tryptophan metabolism and its downstream effects in cancer biology.
The A-549 host cell line was originally established from a 58-year-old male patient with lung adenocarcinoma and harbors an oncogenic KRAS mutation, characteristic of aggressive non-small cell lung cancer. These cells display alveolar type II-like epithelial properties and are widely used as a model system for studying lung cancer pathogenesis, drug responses, and metabolic reprogramming. The KRAS-driven background confers distinct signaling dependencies, making A-549 cells particularly relevant for investigating metabolic vulnerabilities and immune evasion mechanisms in lung adenocarcinoma.
KYNU encodes kynureninase, a pyridoxal phosphate-dependent enzyme that hydrolyzes kynurenine to anthranilic acid in the kynurenine pathway of tryptophan degradation. Pro-inflammatory cytokines such as IFN-??, TNF-??, and IL-1?? upregulate KYNU transcription via STAT1 and NF-??B. Anthranilic acid is a precursor for 3-hydroxyanthranilic acid, which leads to NAD+ synthesis, while kynurenine accumulation can activate the aryl hydrocarbon receptor (AhR), inducing targets like CYP1A1. KYNU thus integrates tryptophan catabolism with immune modulation and NAD+ metabolism, interacting with TDO, IDO, and kynurenine aminotransferases.
In A-549 lung adenocarcinoma cells, KYNU disruption likely causes kynurenine accumulation, shifting metabolism toward AhR activation and reducing NAD+ production. This may enhance immunosuppressive AhR signaling in the tumor microenvironment, relevant to immune evasion in KRAS-mutant lung cancer. Altered NAD+ levels can affect redox balance and cell survival, highlighting metabolic vulnerabilities. This knockout model enables dissection of kynurenine pathway dynamics in oncogenic signaling and drug resistance.
KYNU Knockout A-549 Polyclonal Cells are suitable for LC-MS-based metabolomic profiling of kynurenine pathway intermediates, kynureninase activity assays, and NAD+/NADH quantification. They enable AhR reporter assays, proliferation and apoptosis studies, and drug sensitivity screens with IDO/TDO or NAD+ inhibitors. Migration and invasion assays can assess metastatic effects. For further details or technical support, please contact Ascent Research.
