The IRGQ Knockout NCI-H1703 Polyclonal Cells are a heterogeneous population of CRISPR/Cas9-edited NCI-H1703 cells carrying targeted disruption of the IRGQ gene. This polyclonal knockout model offers a genetically defined loss-of-function system for studying IRGQ-dependent processes without the selective pressures of single-cell cloning. The product provides a stable, mixed cell population in which IRGQ protein expression is ablated, enabling functional and signaling studies in a lung adenocarcinoma background.
The NCI-H1703 cell line originates from a human lung adenocarcinoma derived from a male smoker and harbors an activating KRAS G12C mutation along with STK11 deficiency. These genetic features make it a clinically relevant in vitro model for KRAS-mutant non-small cell lung cancer, a tumor subtype often associated with metabolic reprogramming and altered mitochondrial quality control. The epithelial origin and tumorigenic properties of NCI-H1703 provide a context in which mitophagy and innate immune responses can be interrogated in conjunction with oncogenic signaling.
IRGQ functions as a mitophagy receptor that selectively recognizes damaged mitochondria through its LIR motif, binding to ATG8 family members MAP1LC3B and GABARAP to promote autophagosome formation and subsequent lysosomal degradation. Its expression is transcriptionally upregulated by interferon-?? via STAT1 and IRF1, thereby connecting immune activation to mitochondrial homeostasis. IRGQ interacts with mitochondrial import receptors TOM70 and TOM20 and the ubiquitin kinase PINK1, placing it downstream of mitochondrial depolarization and the PINK1-Parkin pathway. Downstream effects include regulation of autophagosome-lysosome fusion, modulation of the NLRP3 inflammasome, and attenuation of the cGAS-STING pathway, linking mitochondrial clearance to innate immune signaling.
In NCI-H1703 cells, IRGQ knockout disrupts interferon-??-inducible mitophagy, potentially altering mitochondrial turnover and function under stress conditions relevant to KRAS-driven tumorigenesis. Given that STK11 loss and KRAS mutations converge on altered metabolism and immune evasion, this model is valuable for dissecting how mitochondrial quality control influences tumor cell survival, inflammatory responses, and sensitivity to chemotherapeutics or targeted agents. The polyclonal nature preserves population-level heterogeneity, making it suitable for studies requiring a representative cellular pool rather than a clonal isolate.
Researchers can utilize these cells for a range of experimental approaches, including Western blotting and RT-qPCR to assess protein and transcript changes, immunofluorescence with MitoTracker staining to visualize mitophagy, co-immunoprecipitation to probe IRGQ interaction partners, mitophagy flux assays coupled with flow cytometry, and cGAS-STING pathway activation assays. Additional applications include cell proliferation and drug sensitivity screening to evaluate therapeutic responses, as well as migration assays to study metastatic potential. These tools support investigations in autophagy research, immuno-oncology, and mitochondrial biology. For further inquiries, please contact Ascent Research.
