The IL1RAP Knockout NCI-H1975 Polyclonal Cells are a ready-to-use CRISPR/Cas9-edited polyclonal knockout cell population, offered as a mixed population of edited cells carrying disruptions in the IL1RAP gene. This product provides a genetically defined loss-of-function model derived from the NCI-H1975 non-small cell lung cancer cell line, enabling investigation of interleukin-1 (IL-1) coreceptor function without isolation of single-cell clones. The pooled polyclonal format retains population-level heterogeneity, facilitating robust and reproducible experimental designs when compared to clonal isolates.
The host cell line, NCI-H1975, is a well-characterized human lung adenocarcinoma epithelial line originating from a non-smoker female and harboring both L858R and T790M mutations in the epidermal growth factor receptor (EGFR). This genetic background renders the cells dependent on EGFR signaling and sensitive to tyrosine kinase inhibitors, while also exhibiting a basal inflammatory profile. As an established model for non-small cell lung cancer (NSCLC), NCI-H1975 is extensively employed to study tumor cell biology, drug resistance, and the interplay between oncogenic drivers and the tumor microenvironment.
IL1RAP (interleukin-1 receptor accessory protein) functions as an obligate coreceptor for IL-1 family cytokines, including IL-1??, IL-1??, IL-33, and IL-36. Upon cytokine engagement, IL1R1 heterodimerizes with IL1RAP, creating a signaling-competent receptor complex that recruits the adaptor MYD88 and the kinases IRAK1 and IRAK4. This initiates two major branches: the NF-??B pathway, mediated through TRAF6, TAK1, and IKK, leading to nuclear translocation of RELA, and the MAPK cascade, activating JNK, p38, and ERK. As a result, IL1RAP-dependent signaling drives expression of downstream pro-inflammatory genes such as IL6, IL8, and PTGS2, as well as negative regulators like IL1RN, SIGIRR, and TOLLIP that fine-tune the response. The coreceptor thus stands at the nexus of multiple inflammatory axes, integrating signals from diverse IL-1 family ligands.
In the context of NCI-H1975 cells, IL1RAP knockout is particularly significant given the established role of chronic inflammation in NSCLC progression. IL-1?? signaling, for instance, has been implicated in promoting an immunosuppressive tumor microenvironment, enhancing angiogenesis, and conferring resistance to EGFR-targeted therapies. Disruption of IL1RAP in this EGFR-mutant background allows researchers to dissect how IL-1-driven NF-??B and MAPK activation cooperates with oncogenic EGFR signaling to shape tumor cell proliferation, survival, and inflammatory cytokine secretion. Moreover, this model enables exploration of crosstalk between the IL-1 pathway and other inflammation-associated pathways relevant to lung cancer and comorbidities such as rheumatoid arthritis and atherosclerosis.
The IL1RAP knockout polyclonal population enables mechanistic studies and drug discovery efforts. Assays include IL-1??-induced NF-??B p65 phosphorylation by Western blot, IL-6 ELISA, and RT-qPCR for inflammatory genes. Functional readouts such as EdU proliferation, transwell migration, and xenograft growth can assess IL1RAP’s role in oncogenic behavior. The mixed population is suitable for high-throughput inhibitor screens targeting IRAK4, TAK1, or upstream cytokines. This genetic ablation model provides a clean background for drug validation and comparison with wild-type cells. For further information or custom cell engineering, contact Ascent Research.
