The IFT46 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the human NCI-H1975 lung adenocarcinoma cell line. This product features targeted disruption of the IFT46 gene, eliminating functional protein expression across a heterogeneous cell pool. The polyclonal format avoids clonal biases inherent to single-cell-derived lines, providing a population-level loss-of-function model suitable for bulk biochemical and functional assays.
The host NCI-H1975 line is an epithelial model of non-small cell lung adenocarcinoma, isolated from a female pleural effusion. It harbors oncogenic KRAS G12C and TP53 mutations and is wild-type for EGFR, reflecting a common NSCLC genotype. These tumorigenic and metastatic cells are widely used to study lung cancer biology and therapeutic responses.
IFT46 encodes a core subunit of the intraflagellar transport (IFT) complex B, required for anterograde trafficking and primary cilium assembly. It interacts with IFT-B partners IFT20, IFT52, and IFT88, as well as motor proteins kinesin-2 and dynein-2, to enable ciliary protein delivery. IFT46 functions in the Hedgehog pathway by mediating SMO localization and activation of GLI1 transcription, leading to expression of targets like PTCH1. The gene is regulated by SHH ligand, RFX transcription factors, and FOXJ1, and it also participates in PDGFR-alpha signaling and cell cycle control. Loss of IFT46 disrupts ciliogenesis, attenuates Hedgehog signal transduction, and impairs PDGFR-alpha-mediated responses.
In NCI-H1975 cells, IFT46 knockout provides a platform to interrogate cilia-dependent signaling within a KRAS/TP53-mutant context. It enables exploration of how primary cilium loss influences Hedgehog-driven proliferation, migration, and drug sensitivity, and whether IFT46-dependent pathways intersect with mutant KRAS signaling to modulate tumorigenicity.
Typical applications include immunofluorescence detection of primary cilia (acetylated alpha-tubulin, ARL13B), GLI-luciferase reporter assays, cell proliferation and migration studies, and testing of SMO inhibitors. Complementary Western blotting and RT-qPCR confirm knockout efficacy and transcriptional changes. For additional information, please contact Ascent Research.
