The IRGQ Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the NCI-H1975 human lung adenocarcinoma cell line. This product features targeted disruption of the IRGQ gene, which encodes an immunity-related GTPase involved in autophagy and innate immune responses. The polyclonal pool preserves the cellular heterogeneity of the parental line and provides a robust loss-of-function model for bulk analyses. CRISPR-mediated gene disruption was employed to create a mixed population of cells with IRGQ-inactivating mutations, enabling functional studies without clonal selection bias.
NCI-H1975 is a widely studied non-small cell lung cancer line derived from a non-smoking female with adenocarcinoma. It harbors two activating EGFR mutations: L858R in the kinase domain and T790M in the gatekeeper residue, which together confer constitutive signaling and reduced sensitivity to first-generation EGFR tyrosine kinase inhibitors. These cells retain epithelial morphology and are extensively used to investigate EGFR-driven oncogenesis, drug resistance, and tumor microenvironment interactions.
IRGQ belongs to the immunity-related GTPase family, which is robustly induced by type I and type II interferons. Its expression is transcriptionally activated by the JAK-STAT pathway, primarily through STAT1 and STAT2, downstream of IFNAR1/IFNAR2 receptor engagement. Once produced, IRGQ localizes to intracellular membranes and interacts with key autophagy components LC3B and SQSTM1/p62 to regulate autophagic flux. Upstream signaling through IFNAR1/IFNAR2, JAK1, and TYK2 activates STAT1/2, which in turn promote IRGQ expression. Downstream, IRGQ associates with the autophagy initiation complex (ULK1, ATG13, FIP200) and elongation factors (BECN1, ATG5, ATG7). By modulating autophagy, IRGQ contributes to antimicrobial defense and cellular homeostasis, and its loss may impair autophagic clearance and alter interferon responsiveness.
In NCI-H1975 cells, which carry activating EGFR L858R/T790M mutations, autophagy often sustains survival under targeted therapy. Knockout of IRGQ can abrogate protective autophagy, potentially sensitizing cells to EGFR inhibitors such as osimertinib. Additionally, because IRGQ participates in interferon-induced innate immunity, its depletion may alter tumor cell responses to immune activation. This model therefore enables investigation of autophagy-mediated drug resistance and immune evasion in EGFR-mutant lung adenocarcinoma.
Researchers can utilize this product for autophagy flux analysis via LC3 and SQSTM1 western blotting, interferon-stimulated gene expression profiling by RT-qPCR, and cell viability assays with EGFR TKIs. Protein interaction studies by co-immunoprecipitation and immunofluorescence are also applicable. This polyclonal knockout pool is ideal for studying the intersection of autophagy, innate immunity, and oncogenic signaling in lung cancer. For further information or technical support, please contact Ascent Research.
