The IL13RA1 Knockout NCI-H1975 Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population originating from the NCI-H1975 human lung adenocarcinoma epithelial cell line, in which the IL13RA1 gene has been disrupted to generate a loss-of-function model. This heterogeneous pool of edited cells offers researchers a ready-to-use system for investigating IL13RA1-dependent signaling without the need for single-cell cloning, enabling immediate interrogation of gene function in a relevant cancer background.
The NCI-H1975 host cell line is a well-characterized model of non-small cell lung cancer (NSCLC) that harbors EGFR L858R and T790M mutations, conferring oncogenic dependency and resistance to first-generation EGFR tyrosine kinase inhibitors. These adherent epithelial cells are widely employed in studies of lung adenocarcinoma, cancer cell signaling, and mechanisms of acquired drug resistance. The polyclonal knockout population retains the disease-relevant genetic alterations of the parental line while allowing functional assessment of IL13RA1 loss in a therapeutically relevant context.
IL13RA1 encodes the interleukin-13 receptor subunit alpha-1, which forms a heterodimeric complex with IL4RA upon stimulation by the cytokines IL-13 or IL-4. Ligand engagement activates receptor-associated Janus kinases JAK1 and TYK2, leading to phosphorylation and nuclear translocation of the transcription factor STAT6. Additionally, the activated receptor complex promotes signaling through the PI3K/AKT and MAPK/ERK cascades, instigating downstream phosphorylation of AKT and ERK. This pathway architecture positions IL13RA1 as a critical node linking extracellular cytokine cues to multiple intracellular effector networks that govern cell survival, proliferation, and gene expression.
In the NCI-H1975 model, IL13RA1-mediated signaling may contribute to tumor cell autonomous functions and crosstalk with the tumor microenvironment. Loss of IL13RA1 in these lung adenocarcinoma cells allows dissection of IL-13/IL-4-dependent JAK-STAT, PI3K/AKT, and MAPK/ERK pathway contributions to oncogenic phenotypes. The knockout cells provide a platform to examine how IL13RA1 impacts EGFR inhibitor sensitivity, cell migration, and pro-inflammatory cytokine responses, potentially uncovering resistance mechanisms or paracrine signaling loops relevant to NSCLC progression.
These polyclonal IL13RA1 knockout cells are suited for a broad range of downstream applications, including western blotting or flow cytometry to confirm loss of IL13RA1 protein and attenuated phospho-STAT6 levels, cytokine stimulation assays to measure pathway activation, and cell-based functional assays such as proliferation, migration, and drug sensitivity testing. They also facilitate co-immunoprecipitation studies of the IL13RA1?CIL4RA complex and its downstream effectors, as well as transcriptomic profiling via RNA-seq to map IL13RA1-dependent gene networks. Researchers can use this knockout model in screens for IL13RA1-targeted therapeutics or to explore its role in the lung adenocarcinoma tumor microenvironment. For further information, please contact Ascent Research.
