The IFRD1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population of NCI-H1975 human lung adenocarcinoma cells with targeted disruption of the IFRD1 gene. This polyclonal format provides a heterogeneous pool of edited cells, eliminating single-cell cloning bottlenecks and enabling pooled loss-of-function studies. The knockout model serves as a versatile tool for investigating IFRD1-dependent transcriptional regulation in a clinically relevant non-small cell lung cancer context.
NCI-H1975 is a female-derived lung adenocarcinoma epithelial cell line that carries activating EGFR L858R/T790M and PIK3CA G118D mutations. These genetic alterations drive oncogenic signaling and are hallmarks of aggressive lung adenocarcinoma with acquired resistance to first-generation EGFR inhibitors. The cell line retains epithelial morphology and clinically relevant sensitivity to third-generation tyrosine kinase inhibitors, offering a robust platform for functional genomics.
IFRD1 encodes a transcriptional coregulator that represses gene expression by recruiting histone deacetylase complexes, including HDAC1 and HDAC2, to target promoters. It interacts with SIN3A and myogenic regulators MYOD1 and MEF2C, and is induced by interferon-gamma via STAT1 downstream of IFNGR, and by TGFB1 through SMAD2/3. IFRD1 modulates transcription of MYOD1, MYOG, and cell cycle regulators, linking it to myogenesis, neural development, and stress responses. In the context of cancer, IFRD1 may influence HDAC-targeted genes involved in proliferation and differentiation.
In the NCI-H1975 background, IFRD1 knockout provides a physiologically relevant model to study how loss of this coregulator intersects with oncogenic EGFR and PIK3CA signaling. The involvement of IFRD1 in TGF-beta and interferon pathways suggests its deletion could impact EMT, cell cycle progression, and drug sensitivity. The polyclonal population avoids clonal artifacts, enabling robust analysis of population-level transcriptional and phenotypic changes.
Applications include investigating EGFR-mutant lung adenocarcinoma biology, EMT, drug resistance mechanisms, and transcriptional regulation. Key assays include Western blotting, RT-qPCR, RNA-seq, and ChIP-qPCR for molecular characterization, as well as cell proliferation, migration, and drug sensitivity assays (e.g., osimertinib) for functional studies. For additional information, please contact Ascent Research.
